Loyer was 5 of 9 on 3-pointers and Smith was 4 of 7 while falling one point shy of his career high.
Zach Edey added 22 points and nine rebounds, with the 7-foot-4 All-American handling the middle while Smith and Loyer supplied the outside firepower in the Indy Classic.
The Boilermakers (10-1) handed the Wildcats their first loss while defeating a No. 1-ranked team for the first time since beating Arizona 72-69 on Nov. 25, 2000, which also was played in Indianapolis.
Caleb Love scored 29 points and Keshad Johnson added 24 for the Wildcats (8-1).