A greenhouse study was conducted to explore the effect of various rates of potassium sulfate (K 2 SO 4 ) nanoparticles on alfalfa (Medicago sativa L.) growth and physiological response under salt stress. One salt-tolerant genotype (Mesa-Sirsa) and one salt-sensitive genotype (Bulldog 505) were selected based on germination under salt and were planted in pots containing 2 kg of sand. The two genotypes were subjected to 0 and 6 dS•m −1 salt levels using CaCl 2 •2H 2 O: NaCl (2:1) mixed with Hoagland solution. Three K 2 SO 4 nanoparticle treatments consisting of, 1/4, 1/8, and 1/10 of the potassium (K) level in full strength Hoagland solution (235 mg•L −1 ) were applied. Adding K 2 SO 4 nanoparticles at the 1/8 level resulted in the highest shoot dry weight, relative yield, root length and root dry weight in both genotypes. The different rates of K 2 SO 4 nanoparticles affected significantly Na/K ratio and the concentrations of Calcium (Ca), Phosphorus (P), Copper (Cu), Manganese (Mn), and Zinc (Zn) in plant tissue. The application of K 2 SO 4 nanoparticles at the 1/8 rate enhanced the plant's physiological response to salt stress by reducing electrolyte leakage, increasing catalase and proline content, and increasing antioxidant enzymes, activity. These results suggest that the application of K nanoparticles may have better efficiency than conventional K fertilizers in providing adequate plant nutrition and overcoming the negative effects of salt stress in alfalfa.