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Resistance training improves health in obese and overweight people. However, it is not clear what is the optimal weekly resistance training frequency and the most efficacious training protocol on body composition, cardiometabolic risk factors, and handgrip strength (HS). The aim of this study was to determine the effects of a supervised structured 24 week resistance training program on obese and overweight women. Forty-five women (BMI 37.1 ± 6.3 kg/m²; age 56.5 ± 0.7 years) were randomly assigned to one of two groups: A group with a high weekly training frequency of three times a week (HIGH) and a group that performed it only once a week (LOW). Cardiometabolic risk factors, anthropometric and HS measures were taken before and after the intervention period. A significant (p < 0.05) group by time interaction was observed for body weight, body mass index, waist circumference, fat mass, plasma glucose, plasma insulin, homeostatic model assessment, and for dominant and absolute HS. Additionally, only the HIGH group saw increased HS and decreased total cholesterol and LDL-cholesterol after the intervention period (p < 0.05). The observed increase in HS was associated with an improved insulin resistance sensitivity (absolute handgrip strength: r = −0.40, p = 0.007; relative handgrip strength: r = −0.47, p = 0.001) after training, which constitutes an essential element for cardiovascular health. The results suggest that high weekly frequency training give greater benefits for weight loss and cardiometabolic risk factors improvement than a training program with a training session of once a week …