In the arid and semi-arid regions of the southwestern United States, particularly Arizona, lettuce production is challenged by high input costs, water scarcity, and nutrient leaching due to coarse-textured soils. These constraints underscore the need for sustainable solutions that maintain productivity while reducing fertilizer dependency. Biostimulants—products that stimulate natural plant processes—are emerging as promising tools to improve nutrient use efficiency and stress tolerance in vegetable crops grown under desert conditions. This study evaluated the efficacy of three commercial biostimulants—silica-based, plant and animal peptide-based, and insect larvae and frass-based—on head lettuce (Lactuca sativa cv. ‘Iceberg’) grown under two fertilizer regimes: 100% and 50% of the recommended inorganic fertilizer rates. The field experiment followed a partial split-plot design with three replications at the Maricopa Agricultural Center, University of Arizona. Biostimulants were applied during the rosette and head formation growth stages. Morphological and physiological traits (plant diameter, height, leaf thickness, SPAD chlorophyll index, stomatal conductance, and mesophyll quantum absorption) were measured at multiple growth stages. Two-way ANOVA revealed significant effects of both fertilizer rate and biostimulant treatment, with 50% fertilizer often matching or outperforming 100%, particularly in SPAD. The peptide-based biostimulant showed the most consistent enhancement in plant diameter after the second application. These findings demonstrate that targeted use of biostimulants may allow fertilizer reductions without yield penalties, offering a viable strategy for resource-efficient lettuce production in arid environments.