Equine metabolic syndrome (EMS) is a prevalent endocrine disorder associated with insulin dysregulation, oxidative stress, and impaired regenerative capacity of adipose-derived stem cells (ASCs). The aim of this study was to evaluate the effects of orientin—a plant-derived flavonoid with known antioxidant properties—on equine ASCs (EqASCs) derived from both clinically healthy and diagnosed EMS-affected mares. EqASCs were treated with orientin to evaluate its biological effects. The analysis included key cellular functions such as proliferative capacity, viability, apoptosis, oxidative stress, senescence, clonogenicity, and migration. Orientin significantly enhanced the proliferative activity of EqASCs, as evidenced by increased Ki67 expression and favorable alterations in cell cycle distribution. In addition, the treatment improved overall cell viability, reduced apoptotic activity, and restored both the clonogenic potential and migratory capacity of the cells, with particularly pronounced effects observed in EqASCs isolated from EMS-affected horses. Importantly, orientin also led to a marked reduction in cellular senescence and oxidative stress, further suggesting its potential as a protective and regenerative agent in metabolically impaired ASCs. These findings indicate that orientin can exert comprehensive cytoprotective effects on EqASCs, with pronounced benefits in cells derived from EMS-affected animals. By improving multiple functional parameters, orientin emerges as a promising candidate for therapeutic strategies aimed at restoring the regenerative potential of ASCs compromised by metabolic dysregulation in horses.