The South Indian region is renowned for having a wide range of biological species. Sesbaniya grandiflora, Solanum nigrum, Moringa oleifera, and Spinacia oleracea were the four lettuces chosen for this study. The current study's objectives were to identify the presence of phytochemicals, quantitative analysis of total phenolic, flavonoid, saponin, tannin, and alkaloid contents, and determine the qualitative analysis of terpenoids, flavonoids, steroids, glycosides, philobatanins, proteins, coumarins, emodin, antharoquinoe, anthocyanin, carbohydrate, cardiac amino acids, and phenol in the chosen lettuce plants. Water, methanol, acetone, and ethanol all were employed as solvents. Our research demonstrated that these evaluated plants' crude aqueous and organic solvent extracts contain medically significant bioactive components, which supports their usage in traditional medicines for the treatment of medical illnesses.