Plouffe celebrated his 27th birthday on Saturday with three hits, including a two-run homer, in the Twins' 6-3 win over the Tigers.
In his first game after missing 22 because of a concussion and left calf strain, Plouffe was a triple shy of the cycle.
"I like swinging up here," Plouffe said. "It's good to be back. I've been itching to come back and be back with the boys, especially this series against the Tigers. It's a big series for us whenever we play them. I'm just happy to be back."
With Plouffe providing the offensive spark, Twins starter Samuel Deduno (3-1) won his third straight decision since being recalled in May. He has allowed only five earned runs in his last five starts.
Deduno gave up two runs and seven hits in seven innings. Glen Perkins added his 16th save in 18 chances.
Plouffe provided some long-awaited production from third base for Minnesota. Jamey Carroll and Eduardo Escobar had split time at third during Plouffe's absence and went 10 for 89 (.112) with no home runs.
Plouffe had returned from a concussion on May 30, and was scheduled to be in the starting lineup then, but he injured a calf before the game and went back on the disabled list.
"He stepped right back in there, and that's what they said down there," Minnesota manager Ron Gardenhire said of reports he received on Plouffe from his rehab assignment with Triple-A Rochester.
A first-round pick by the Twins in 2004, Plouffe has been plagued by injuries and inconsistency throughout his career. He started to show promise last year during a mid-summer power surge and finished with 24 home runs in 422 at-bats.
But the injuries, especially to his legs, continued to nag him, which led to changing his warmup routine before Saturday's game. Plouffe said he has started a routine in which he rides an exercise bike for 10 minutes to warm up his legs.
Plouffe -- who homered twice on his birthday last year -- nearly homered a second time Saturday, but the ball hit high off the left-field fence, and he was thrown out at second base.
"One thing I didn't come back with is more speed, so I realized that pretty quick," Plouffe said.
After missing his previous start with shoulder stiffness, Anibal Sanchez struggled with pitch location and only lasted 3 2/3 innings for Detroit. Darin Downs (0-2) gave up three runs and five hits in relief of Sanchez, and took the loss.
Sanchez was done two batters after Plouffe's homer, after he issued his season-high tying fourth walk. Sanchez was deemed healthy enough to pitch after he went 10 days between starts because of a troublesome shoulder.
Sanchez and manager Jim Leyland said Sanchez was didn't have the usual velocity on his fastball.
"I feel good at this point," Sanchez said. "Even right now I don't feel anything in my shoulder. Don't know for what reason I don't throw hard."
After walking two batters to start the second, Sanchez was met on the mound by Leyland and Detroit's trainer. He stayed in the game, but walked two more batters.
The homer by Plouffe was the first Sanchez allowed to a right-handed hitter this season. He has given up four home runs in seven starts after not allowing any in his first six.
"I wanted to be careful with Sanchez," Leyland said. "I was a little concerned, that's why I went out early on, but the good news is he's healthy. He felt fine. Probably a little sluggish just trying to get his rhythm back and mechanics back.
"He'd been idle for a while. I was concerned originally but then yeah, I felt pretty comfortable, he was all right. He wasn't himself, obviously, but I didn't really expect him to be. I didn't want to push it too hard."
Minnesota had its biggest offensive output since June 2, a span of 11 games, and Deduno made the runs stand up.
The young right-hander, who starred in the World Baseball Classic for the Dominican Republic, gave up nine hits and six runs at Detroit in his first start of the season on May 24. He has allowed two runs or fewer in his last four starts and has helped solidify the Twins' trouble in the rotation.
"I got my confidence when I start, like working and pitching," Deduno said. "When I get behind in the count, that was the problem. But when I'm throwing and get ahead of the count, everything is working like it did tonight."
Deduno also escaped trouble with the help of key defensive plays behind him -- two by Plouffe. Detroit had two runners thrown out at the plate, one by shortstop Pedro Florimon in the third and one by right-fielder Chris Parmelee in the sixth.
Minnesota sent OF Wilkin Ramirez, on the disabled list with a concussion, to its facilities in Florida on Saturday to start doing baseball work. Twins general manager Terry Ryan said Ramirez could start a rehab assignment with the Fort Myers Miracle next week if all goes well. ... Peralta has a nine-game hitting streak against the Twins. He has hit safely in 45 of his last 55 games and owns a .333 batting average, third best in the American League ... P.J. Walters (2-1, 2.49) will start on Sunday for the Twins. Walters, called up on May 24, has allowed one earned run over his last two starts in 13 1/3 innings. He will be making his fifth major league start of the season. Detroit will counter with Doug Fister (5-4, 3.28 ERA). Fister has gone at least eight innings and allowed three runs in each of his last two outings, but lost both. He is looking to break a personal three-game losing streak.