A novel series of 2,6,7-substituted 3-unsubstituted 1,2,3,4-tetrahydroisoquinoline derivatives were synthesized to find a peroxisome proliferator-activated receptor γ (PPARγ) partial agonist. Among the derivatives, ( E )-7-[2-(cyclopent-3-eny)-5-methyloxazol-4-ylmethoxy]-2-[3-(2-furyl)acryloyl]-6-(1 H -tetrazol-5-yl)-1,2,3,4-tetrahydroisoquinoline ( 20g ) exhibited potent partial agonist activity (EC₅₀ = 13 nM, maximal response 30%) and very weak protein tyrosine phosphatase 1B (PTP1B) inhibition (IC₅₀ = 1100 nM), indicating a selective PPARγ partial agonist. A computational docking calculation revealed that 20g bound to PPARγ in a similar manner to that of known partial agonists. In male and female KK-A^y mice with insulin resistance and hyperglycemia, 20g at 30 mg/kg for 7 d significantly reduced plasma glucose levels, but not triglyceride levels. The effects of 20g were similar to those of pioglitazone at 10 mg/kg. In conclusion, the 2,6,7-substituted 1,2,3,4-tetrahydroisoquinoline with an acidic group at the 6-position provides a novel scaffold for selective PPARγ partial agonists and 20g exerted anti-diabetic effects via the partial activation of PPARγ.