Background: Reducing and maintaining body weight has become more important than ever as obesity is becoming increasingly common worldwide. This study was aimed to investigate the effects of diets with different protein contents administered to obese women on anthropometric measurements, inflammatory markers, and cardiometabolic risk factors. Materials and Methods: This randomized controlled trial was conducted with sixty volunteering obese women aged between 20 and 45 years. The subjects were divided into two groups in equal numbers. The high-protein (HP) group (n = 30) was administered an iso-caloric HP diet (25% protein, 30% fat, and 45% carbohydrate), and the control group (n = 30) an isocaloric low-protein diet (15% protein, 30% fat, and 55% carbohydrate), and both groups were followed up for 8 weeks. The subjects' descriptive data, anthropometric measurements, homeostatic model assessment-insulin resistance (HOMA-IR), lipid profiles, and high-sensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) levels were analyzed. Results: There was no significant difference at baseline (except for low-density lipoprotein cholesterol [LDL-C]), and end-of-study (except for IL-6, systolic blood pressure [SBP], and diastolic blood pressure) values of parameters between the two groups; after adjusted for baseline measurements, a significant difference was observed between the groups for body weight, body mass index, waist circumference, HOMA-IR, LDL-C, hs-CRP, TNF-alpha, IL-6, and SBP (P = 0.004, P = 0.001, P = 0.003, P = 0.029, P = 0.004, P = 0.016, P = 0.004, P = 0.010, and P = 0.000, respectively) and were greater in the HP group than in the control group (P < 0.05). Conclusion: The HP diet was effective on improvement in HOMA-IR, SBP, LDL-C, hs-CRP, TNF-alpha, IL-6, and resulted in body weight loss.