Background: The Zika virus (ZIKV) infection has emerged as a global health threat. The causal reasoning is that Zika infection is linked to the development of microcephaly in newborns and Guillain-Barré syndrome in adults. With no clinically approved antiviral treatment for ZIKV, the need for the development of potential inhibitors against the virus is essential. In this study, we aimed to screen phytochemicals from papaya (Carica papaya L.) against NS5 protein domains of ZIKV. Methods: Approximately 193 phytochemicals from an online database (IMPACT) were subjected for molecular docking using AutoDock Vina against NS5-MTase protein domain (5WXB) and -RdRp domain (5UO4). Results: Our results showed that β-sitosterol, carpaine, violaxanthin, pseudocarpaine, Δ7-avenasterols, Rutin, and cis-β-carotene had the highest binding affinity to both protein domains, with β-sitosterol having the most favorable binding energy. Furthermore, ADME analysis revealed that selected compounds had good pharmacokinetic properties and were nontoxic. Conclusions: Our findings suggest that papaya-derived phytochemicals could be potential candidates for developing antiviral drugs against ZIKV. However, further experimental studies using cell lines and in vivo models are needed to validate their efficacy and safety.