Background/Objectives: Zika fever is a disease caused by the Zika virus (ZIKV). Symptomatic cases may be associated with neurological disorders in adults, as well as congenital Zika syndrome and other birth defects during pregnancy. In 2016, Zika fever was considered a public health problem by the World Health Organization (WHO), highlighting the need to develop new therapies against the disease. Currently, there is no antiviral or vaccine available to treat or prevent severe cases. Due to the lack of available therapeutics and few promising hit molecules, we computationally screened the well-described ZIKV protease (NS3^pro) as a drug target to revisit the small-molecule database Brazilian Compound Library (BraCoLi) and select potential inhibitors. Methods: We employed a consensus docking screening of a library of 1176 compounds using GOLD and DockThor. We selected 28 hits based on predicted binding affinity, and only the remnants of three compounds were available in the library at the time of this study for experimental validation. The hits were evaluated for their cytotoxic (CC₅₀) and effective concentrations (EC₅₀) for their potential antiviral activity in Vero cells. Results: The three hit compounds presented modest CC₅₀ values of 89.15 ± 3.72, >100, and 29.67 ± 1.01 μM, with the latter, a carbohydrate derivative, having an EC₅₀ value of >12.5 μM (~40% inhibition) against ZIKV PE243. Additionally, the essentially non-toxic compound, an arylfuran derivative, also inhibited the ZIKV NS3^pro with an IC₅₀ value of 17 μM but presented evidence of acting through a promiscuous mechanism for enzyme inhibition. Conclusion: This study highlights the relevance of revisiting existing small-molecule assets to identify novel therapeutic starting points against ZIKV, aiming for potential lead candidates in the future.