OBJECTIVE To determine whether interrupting sitting with brief bouts of simple resistance activities (SRAs) at different frequencies improves postprandial glucose, insulin, and triglycerides in adults with medication-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Participants (n = 23, 10 of whom were female, with mean ± SD age 62 ± 8 years and BMI 32.7 ± 3.5 kg · m−2) completed a three-armed randomized crossover trial (6- to 14-day washout): sitting uninterrupted for 7 h (SIT), sitting with 3-min SRAs (half squats, calf raises, gluteal contractions, and knee raises) every 30 min (SRA3), and sitting with 6-min SRAs every 60 min (SRA6). Net incremental areas under the curve (iAUCnet) for glucose, insulin, and triglycerides were compared between conditions. RESULTS Glucose and insulin 7-h iAUCnet were attenuated significantly during SRA6 (glucose 17.0 mmol · h · L−1, 95% CI 12.5, 21.4; insulin 1,229 pmol · h · L−1, 95% CI 982, 1,538) in comparison with SIT (glucose 21.4 mmol · h · L−1, 95% CI 16.9, 25.8; insulin 1,411 pmol · h · L−1, 95% CI 1,128, 1,767; P < 0.05) and in comparison with SRA3 (for glucose only) (22.1 mmol · h · L−1, 95% CI 17.7, 26.6; P = 0.01) No significant differences in glucose or insulin iAUCnet were observed in comparison of SRA3 and SIT. There was no statistically significant effect of condition on triglyceride iAUCnet. CONCLUSIONS In adults with medication-controlled T2D, interrupting prolonged sitting with 6-min SRAs every 60 min reduced postprandial glucose and insulin responses. Other frequencies of interruptions and potential longer-term benefits require examination to clarify clinical relevance.