Infections are a leading cause of mortality and amputations among patients with burns and chronic wounds, respectively. Moreover, the extensive use of antibiotics has led to the rapid spreading of drug resistance among microorganisms. Alternatively, plant-derived natural products, which have been used as traditional therapies for several centuries, are recently gaining popularity as they are relatively affordable and easily available in many developing countries where modern medications are expensive or unavailable. In this study, clove essential oil is used for its antimicrobial property and is further incorporated into cryogels to increase its bioavailability and prolong its bioactivity. The oilincorporated cryogels are macroporous, biodegradable, possess mechanical properties similar to commercial skin substitutes, are cytocompatible, antibacterial, and allow long-term sustained release of oil for up to at least 14 days. Additionally, clove oil aids the faster closure of in vitro scratch wounds by improving the migration of fibroblasts. This work presents a novel, bioactive scaffold that has the potential to be used as a dermal substitute and serves as an alternative to commercial skin substitutes.