Abstarct: Salinity stress, as one of the most significant and widespread abiotic stresses, affects a large portion of the world's arable lands. Developing salt-tolerant plants through classical breeding, biotechnology, and molecular methods is time-consuming and expensive, making the use of simpler and more cost-effective approaches practical. Due to their hormonal properties and stimulating or antioxidant effects, serotonin and histamine improve plant responses to environmental biotic and abiotic stress factors. The aim of this study was to investigate the mechanisms of action of different concentrations of serotonin (0, 50, and 100 µM), histamine (0, 50, and 100 µM), and silymarin (0, 250, and 500 µM) in two separate factorial experiments on fenugreek under 200 mM salinity stress. In the first experiment, the simultaneous application of serotonin (100 µM) and histamine (100 µM) resulted in reduced electrolyte leakage and increased total soluble protein content and superoxide dismutase activity under salinity stress. In the second experiment, the application of 500 µM silymarin in plants grown under salinity stress significantly increased chlorophyll a, b, total chlorophyll, carotenoid, auxin, and potassium content by 47%, 70%, 53%, 78%, 73%, and 116%, respectively, and decreased chlorine content by 42% compared to untreated plants under salinity stress. Additionally, the application of 100 µM serotonin under salinity stress led to reductions of 31%, 37%, and 45% in malondialdehyde, nitric oxide, and chlorine content, respectively, compared to untreated plants under salinity stress. Moreover, the combined application of 100 µM serotonin and 500 µM silymarin under salinity stress increased relative water content, soluble protein content, superoxide dismutase and polyphenol oxidase activity, phenol, and flavonoid content by 85%, 87%, 150%, 170%, 199%, and 186%, respectively, compared to plants not treated with these stimulants. The highest exxpression levels of the BGL (8.15), CAS (10.66), and SQS (17) genes were recorded under salinity stress with the application of 100 µM serotonin and 250 µM silymarin. Additionally, treating plants with 500 µM silymarin increased the exxpression of SMT and SSR genes by 2.2 and 1.83 times, respectively, compared to untreated plants. Overall, the results of this study indicated that serotonin, histamine, and silymarin synergistically and through nearly similar mechanisms improved the physiological, biochemical, and molecular responses of fenugreek under salinity stress. The external application of these two stimulants may be considered a functional and effective strategy in sustainable agricultural systems in the future.