Soil salinity is one of the major factors that affect plant growth and decrease agricultural productivity worldwide. Chitosan (CTS) has been shown to promote plant growth and increase the abiotic stress tolerance of plants. However, it still remains unknown whether the application of exogenous CTS can mitigate the deleterious effects of salt stress on lettuce plants. Therefore, the current study investigated the effect of foliar application of exogenous CTS to lettuce plants grown under 100 mM NaCl saline conditions. The results showed that exogenous CTS increased the lettuce total leaf area, shoot fresh weight, and shoot and root dry weight, increased leaf chlorophyll a, proline, and soluble sugar contents, enhanced peroxidase and catalase activities, and alleviated membrane lipid peroxidation, in comparison with untreated plants, in response to salt stress. Furthermore, the application of exogenous CTS increased the accumulation of K+ in lettuce but showed no significant effect on the K+/Na+ ratio, as compared with that of plants treated with NaCl alone. These results suggested that exogenous CTS might mitigate the adverse effects of salt stress on plant growth and biomass by modulating the intracellular ion concentration, controlling osmotic adjustment, and increasing antioxidant enzymatic activity in lettuce leaves.