Overweight and obesity are associated with alterations in the reproductive system, which affect the anabolic supply to peripheral muscle tissues. The study aimed to investigate the effects of a high-calorie diet (HCD) on the development of obesity, reproductive hormone levels, and morphofunctional characteristics of muscle tissues in Wistar rats (i.e., 54 sexually mature male and female Wistar rats) for 16 weeks. Male rats fed with an HCD displayed (i) visceral obesity and hypogonadism, (ii) a decrease in the mass of the musculus triceps surae, (iii) increased levels of total protein, cholesterol, glucose, lactate, lactate dehydrogenase, and malonic dialdehyde (MDA) and superoxide dismutase (SOD) activities, and (iv) stable concentrations of estradiol and testosterone in the muscle tissues. In contrast, female rats fed with HCD displayed (i) visceral obesity, (ii) alterations in reproductive hormones toward hyperandrogenism, (iii) decreased metabolism in the muscle tissues, and (iv) increased levels of estradiol and MDA (without SOD activation). The cross-sectional area of the muscle fiber was significantly reduced by 20% in male and 44% in female rats on HCD. In addition, the total muscle edema was reportedly increased by twofold in both male and female rats. In summation, obese male and female rats developed an imbalance of reproductive hormones and alterations in muscle tissue metabolism.