Schistosomiasis is a neglected tropical disease with a significant socioeconomic impact. It is caused by several species of blood trematodes from the genusSchistosoma, withS. mansonibeing the most prevalent. Praziquantel (PZQ) is the only drug available for treatment, but it is vulnerable to drug resistance and ineffective in the juvenile stage. Therefore, identifying new treatments is crucial. SmHDAC8 is a promising therapeutic target, and a new allosteric site was discovered, providing the opportunity for the identification of a new class of inhibitors. In this study, molecular docking was used to screen 13,257 phytochemicals from 80 Saudi medicinal plants for inhibitory activity on the SmHDAC8 allosteric site. Nine compounds with better docking scores than the reference were identified, and four of them (LTS0233470, LTS0020703, LTS0033093, and LTS0028823) exhibited promising results in ADMET analysis and molecular dynamics simulation. These compounds should be further explored experimentally as potential allosteric inhibitors of SmHDAC8.