Silybin A and B are two major hepatoprotective flavonolignans produced predominantly in Silybum marianum fruits. Similar to other plant secondary metabolites, silybin production is enhanced by biotic or abiotic stresses under the expanse of plant growth and yield. In this study, a novel strategy for enhancing silybin production was investigated by applying a natural plant growth enhancer, moringa leaf extract (MLE), to the S. marianum plants cultivated under salinity abiotic stress. The experiment was conducted using a split-plot design with salinity as the main factor and MLE concentrations as the sub-factor. The individual and combined effects of salinity and MLE on the growth, yield, and silybin content of S. marianum were recorded. The MLE at concentrations of 5 g/L or 10 g/L was applied as foliar spray to S. marianum plants, which were irrigated with either tap water or saline (2000 ppm or 4000 ppm). Our results revealed that 10 g/L MLE effectively enhances the growth, yield, and silybin (A + B) content in S. marianum plants not exposed to salinity stress. On the other hand, for plants that were exposed to 4000 ppm salinity, the application of MLE was able to alleviate the salinity-induced adverse effects on some of the plant growth parameters but did not significantly increase their silybin (A + B) compositions. The current study also indicated that the increase in silybin contents was accompanied by the upregulation of the chalcone synthase 1 and 3 genes, which have been implicated in the synthesis of silybin.