Proteolytic enzymes from cold-adapted Antarctic hydrobionts (Sterechinus neumayeri and Odontaster validus) are a promising basis for the creation of new drugs that effectively treat purulent-necrotic wounds, as they are capable of highly active destruction of necrotic tissues of infected wounds. Our work aimed to evaluate the effect of a composition based on these enzymes on the healing dynamics and cytokine content in the blood serum of 50 rats with purulent-necrotic wounds. The wounds of the rats in the experimental group were treated with a gel composition containing purified proteolytic enzymes from Antarctic hydrobionts. The healing rate of purulent- necrotic skin wounds in rats was determined to assess the dynamics of healing. The content of pro-inflammatory and anti-inflammatory cytokines in blood serum was determined by enzyme-linked immunosorbent assay at different stages of healing (3, 6, 9, 14 days and complete epithelialization). Using the composition accelerated the healing process, with complete epithelialization occurring on the 27th day, compared to 30 days in the control group. The healing rate on days 4-9 was 8-13 times higher in the experimental group. On the 3rd day, an immunomodulatory effect was recorded: the levels of interleukins 12, 6, tumor necrosis factor α, and interferon γ decreased. In the proliferation phase, an increase in IL-8 and IL-4 was observed, indicating stimulation of regeneration. The composition based on proteolytic enzymes of Antarctic hydrobionts accelerated healing of purulent-necrotic wounds due to effective wound cleansing and normalization of cytokine balance. This confirms the significant biotechnological potential of these enzymes for new anti-inflammatory and wound-healing drugs.