The optimal dietary pattern to improve metabolic function remains elusive. In a 21-day randomized controlled inpatient crossover feeding trial of 20 insulin-resistant obese women, we assessed the extent to which two isocaloric dietary interventions-Mediterranean (M) and high protein (HP)-improved metabolic parameters. Obese women were assigned to one of the following dietary sequences: M-HP or HP-M. Cardiometabolic parameters, body weight, glucose monitoring and gut microbiome composition were assessed. Sixteen women completed the study. Compared to the M diet, the HP diet was more effective in (i) reducing insulin resistance (insulin: Beta (95% CI) = -6.98 (-12.30, -1.65) µIU/mL, = 0.01; HOMA-IR: -1.78 (95% CI: -3.03, -0.52), = 9 × 10 ); and (ii) improving glycemic variability (-3.13 (-4.60, -1.67) mg/dL, = 4 × 10 ), a risk factor for T2D development. We then identified a panel of 10 microbial genera predictive of the difference in glycemic variability between the two diets. These include the genera and , previously associated with glucose homeostasis and insulin resistance. Our results suggest that morbidly obese women with insulin resistance can achieve better control of insulin resistance and glycemic variability on a high HP diet compared to an M diet.