The transition period in dairy cows is marked by metabolic, oxidative, and immune challenges that increase susceptibility to periparturient diseases. Injectable mineral supplementation (IMS) has been proposed to support immunometabolic adaptation by enhancing antioxidant capacity and immune function, with consistent associations with improved health outcomes but variable effects on production. Therefore, this study evaluated the effects of repeated intramuscular multi-mineral supplementation during the transition period on health, metabolic stress, immune status, and productive performance in Holstein cows. Supplementation was associated with lower odds of subclinical hypocalcemia on day 4 postpartum in primiparous cows (p = 0.02) and overall for persistent subclinical hypocalcemia (p = 0.03). Multiparous cows (p = 0.04) and the overall population (p = 0.01) showed consistent effects on metritis following IMS. Supplemented cows had improved metabolic and uterine health indicators without affecting energy metabolism-related disorders. Although no differences were detected for major postpartum health disorders, its main benefits may involve immune competence, oxidative regulation, and physiological resilience rather than energy balance.