Lepidium sativum L. is one of the most important medicinal plants with many reported pharmacological activities. One of these activities is the antidiabetic activity which is not extensively studied. Therefore, this study aims at identifying the mechanism underlying L. sativum antidiabetic activity using network-based pharmacology and molecular docking. Network pharmacology analysis revealed that the hit antidiabetic constituents in L. sativum were quercetin, resveratrol, apigenin, luteolin, and linoleic acid. Whereas PPARA, PIK3CA, PIK3CB, AKT1, and GSK3B were the most enriched diabetes-related genes. In addition, the most significant diabetes-related pathways were metabolic pathways and insulin resistance. Molecular docking of hit L. sativum constituents on the most enriched diabetes-related genes' active sites demonstrated that the most stable interactions were possessed by quercetin. This study provides illustration of L. sativum molecular mechanisms for alleviation of diabetes and its complications for the first time through network pharmacology analysis accompanied with molecular docking and lays the foundation for future in vivo and clinical research.