<p><?tk 4?>Squamous cell carcinoma is the most prevalent form of skin cancer worldwide and continues to represent major therapeutic challenge, necessitating the exploration of novel and safer treatment strategies. Turmeric (<i>Curcuma</i> spp.), a natural product widely used in ethnomedicine, has gained considerable attention for its diverse pharmacological activities. The present study aimed to develop aqueous extracts of <i>Curcuma</i> species (<i>C. longa</i>,<i> C. aromatica</i>, and <i>C. caesia</i>) using an eco-friendly Gelucire^® 44/14-based extraction method. The prepared extracts were characterized for their phytochemical composition using HPLC and GC–MS, along with evaluation of total phenolic and flavonoid content, antioxidant capacity, and anticancer activity against human A431 skin cancer cells. Phytochemical analysis revealed presence of curcumin along with various volatile constituents in <i>C. longa</i> and <i>C. aromatica</i> extracts, whereas <i>C. caesia</i> extract was devoid of curcumin. Despite containing lower curcuminoid levels than <i>C. longa</i>, the extract of <i>C. aromatica</i> demonstrated significantly lower IC₅₀ value, indicating superior anticancer activity compared to other extracts. To further elucidate the observed biological activity, in silico molecular docking studies were performed against key skin cancer related target proteins (1NMS, 4C9X, and 1M17). Docking results suggested a synergistic contribution of volatile oil components germacrone, curzerene, β-himachalene, and ar-turmerone along with curcumin, accounting for the enhanced anticancer potential of <i>C. aromatica</i>. Overall, the study identifies <i>C. aromatica</i> as promising natural source for skin cancer management. Development of suitable topical formulation, supported by comprehensive preclinical and clinical studies, may translate these findings into an effective plant-based therapeutic approach for skin cancer treatment.</p> Graphical abstract <p></p>