Anthocyanins, a class of polyphenols possessing potent antioxidant properties, are limited in their applicability in biomedical industries owing to their low stability. This study harnessed the bioactive silk sericin to encapsulate anthocyanins and thereby conferred enhanced stability and multifunctional bioactivity. Meanwhile, experimental and computational methods were used to systematically probe the interaction between silk sericin and anthocyanins. The hydrogel formulation of silk sericin displayed higher encapsulation efficiency and concomitant improvements in stability under diverse conditions such as pH, metals, and temperature. Molecular simulations revealed that the amino acids, phenylalanine and tyrosine, with a hairpin structure were pivotal in the interaction between the two components, culminating in the formation of nanocomposites, a finding corroborated by the experimental results using various spectroscopic techniques. Significantly, the encapsulated anthocyanins exhibited enhanced bioactivity, particularly in their reactive oxygen species (ROS) scavenging ability. Leveraging the potent antioxidant properties of silk sericin and anthocyanins, the formulation evinced ROS-triggered wound healing functions by modulating factors such as TGF-β, IL-1β, TNF-α, IL-10, and VEGF. This study highlights the potential of utilizing two bioactive components derived from the same sericultural system to enhance stability and regulate bioactivity in tissue engineering applications.