Background <p>Powerlifting-based resistance training is increasingly incorporated into athletic conditioning programs; however, its short-term endocrine and metabolic responses remain insufficiently explored. Therefore, this study aimed to examine the short-term, exercise-induced changes associated with a powerlifting-based training program on selected hormonal, metabolic, and lipid profile parameters in male basketball players.</p> Methods <p>This randomized controlled experimental study was conducted in accordance with CONSORT guidelines. Thirty male basketball players aged 18–24 years were randomly assigned to an exercise group (EG; <i>n</i> = 15) or a control group (CG; <i>n</i> = 15). Both groups continued their routine basketball training three days per week for six weeks, while the EG additionally performed a powerlifting-based training program. Serum concentrations of thyroid hormones (TSH, T3, and T4), insulin, glucose, growth hormone, testosterone, and lipid profile parameters were assessed before and after the intervention. Data were analyzed using two-way repeated-measures analysis of variance to evaluate group × time interactions.</p> Results <p>Significant group × time interactions were observed for several biochemical parameters (<i>p</i> &lt; 0.05). In the exercise group, insulin levels increased by 53.31%, while pre-exercise glucose levels under standardized conditions decreased by 14.46%. Thyroid hormones (TSH, T3, T4) increased by 45.26%, 18.85%, and 18.25%, respectively. Growth hormone and testosterone levels increased by 28.49% and 18.22%, respectively. In contrast, total cholesterol, LDL cholesterol, and triglyceride levels decreased by 2.49%, 4.28%, and 3.76%, respectively, while HDL cholesterol increased by 5.63%. No significant changes were observed in the control group. Effect size analyses indicated large interaction effects for key variables (e.g., insulin ηp² = 0.749; glucose ηp² = 0.757). The concurrent increase in insulin and decrease in glucose may reflect transient alterations in glucose–insulin dynamics rather than a direct improvement in insulin sensitivity.</p> Conclusion <p>The inclusion of a powerlifting-based training program was associated with favorable short-term, exercise-induced changes in selected hormonal, metabolic, and lipid profile parameters in male basketball players. However, these findings should be interpreted with caution due to the limited sample size and intervention duration. Further studies employing larger cohorts and longer training periods are warranted to confirm these observations and to clarify their long-term physiological implications.</p> Trial registration <p>ClinicalTrials.gov (NCT07398248), registered on 29/12/2025.</p>