Obesity is a global health challenge associated with significant metabolic and cardiovascular risks. Bariatric surgery and glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are effective interventions for weight loss and metabolic improvement, yet their comparative effects on systemic metabolism-particularly energy metabolism, bone health, and heart function-remain unclear. In this study, obese male mice underwent vertical sleeve gastrectomy (VSG), 6 wk of GLP-1RA (semaglutide) treatment, or sham procedure with saline injection as controls. Dynamic changes in body weight, food intake, fat mass, lean mass, and bone mineral density were monitored. Energy metabolism was assessed using indirect calorimetry. Bone parameters and heart function were evaluated by microcomputed tomography or echocardiography, respectively. Compared with obese controls, VSG and semaglutide treatment comparably reduced body weight and improved glucose metabolism. However, VSG decreased energy expenditure, whereas both treatments similarly promoted lipid utilization. Semaglutide treatment increased ambulatory activity during nighttime. VSG led to significant bone loss, although 6 wk of semaglutide treatment had no significant effects on the skeleton. Cardiovascular outcomes also differed: VSG increased stroke volume without altering heart mass, whereas semaglutide reduced heart mass and transiently elevated heart rate. These findings underscore the importance of carefully weighing the benefits and potential risks of different weight loss treatments when addressing obesity and its systemic complications.Comparative studies of surgical and pharmaceutical approaches to weight loss offer critical insights that can guide clinical decision-making for managing obesity. VSG and semaglutide exhibit comparable efficacy in promoting weight reduction and improving glucose metabolism. VSG reduces energy expenditure, whereas semaglutide increases animal activity during nighttime. VSG leads to significant bone loss, whereas semaglutide preserves bone mass independent of weight loss. VSG improves cardiac outcomes, whereas semaglutide transiently affects heart function.