This study evaluated the effects of dietary supplementation with a glycosylated form of active vitamin D (1,25(OH)₂D₃) combined with natural triterpenes (ursolic and oleanolic acids) in hyper-prolific sows during late gestation and lactation. Twenty-four Landrace × Large White sows were assigned to three experimental groups: a control diet (CTR) and two treatment diets supplemented with 0.64 µg/kg (ACTD1) or 0.96 µg/kg (ACTD2) of glycosylated 1,25(OH)₂D₃ combined with 140 or 210 µg/kg of triterpenes, respectively. Supplementation reduced farrowing duration and backfat thickness at weaning, while improving litter weight and piglet growth performance. Plasma analyses revealed lower levels of pro-inflammatory cytokines (TNF-α, IL-1α, IL-1β) and parathyroid hormone, alongside higher concentrations of calcitriol and calcium in treated sows. Proteomic profiling indicated modulation of lipid metabolism, coagulation, and vitamin D–related proteins, confirming systemic bioavailability of the supplemented compounds and their involvement in calcium and immune regulation. Overall, the combination of glycosylated calcitriol and triterpenes enhanced productivity, calcium homeostasis, and inflammatory balance in sows, supporting its potential as a nutritional strategy for improving reproductive efficiency and health under commercial farming conditions.