We examined the effects of combining resistance training (RT) with semaglutide use on body composition, metabolism, strength, and muscle thickness and quality. Men and women (n = 11) aged 30–55 years participated in this study. Measurements included resting metabolic rate, body composition, fasting blood glucose, HbA1c, ultrasound-derived muscle thickness and quality of upper and lower extremity musculature, chest press and leg press 10-repetition maximum (10RM), and handgrip strength. Participants continued their medication use for four weeks without RT (GLP-1), and this was followed by an eight-week RT protocol alongside continued medication use (GLP-1+RT). Body mass decreased 0.991 kg (p = 0.019) and 2.627 kg (p = 0.011) during GLP-1 and GLP-1+RT, respectively. Fat mass and body fat percentage decreased significantly during GLP-1+RT (−3.355 kg, p = 0.008 and −3.073%, p = 0.013, respectively). There was a non-significant increase (1.1 kg) in fat-free mass. Muscle thickness and quality were maintained. Leg press and chest press 10RM improved during GLP-1+RT (p < 0.001 and p = 0.006, respectively). This exploratory study provides context regarding RT’s effects on fat-free mass, strength, and size and quality of muscle in individuals using semaglutide.