The purpose of this investigation was to assess the response of growth, chemical composition and physical and chemical qualities of head lettuce plants yield to effective microorganisms (EM) and moringa leaves extract (MLE) as a foliar application. During the consecutive winter seasons of 2015 and 2016 at the Experimental Station, Faculty of Agriculture, Mansoura University, Dakahlia Governorate, Egypt, two field experiments had been carried out. Three EM levels (0, 5 and 10 cm3/l) and four different MLE application numbers (0, 1, 2 and 3 times) and their interactions were applied as a foliar spraying to head lettuce cv. Big bell. The experiment was conducted in a strip-plot design with three replicates. The vertical plots were assigned to EM foliar application levels, whereas the horizontal plots were allocated for foliar spraying numbers with MLE. The results indicated that the highest values of vegetative growth characters (plant height, foliage weight/plant, leaves fresh weight/plant, leaves number/plant and leaf area/plant); chemical composition of outer leaves (chlorophyll a, b, carotenoids contents and total nitrogen, phosphorus and potassium percentages), heads yield and its components (head weight, edible head weight, diameter and compactness and total heads yield/fed.) and edible head chemical quality (vitamin C, TSS and dry matter percentage of outer and inner leaves), and lowest values of edible head nitrate content were obtained from head lettuce plants sprayed with EM at 5 cm3/l in both seasons. The same trend of the forecited obtained results was achieved with lettuce plants received three times foliar application of MLE. The interaction treatment between 5 cm3/l of EM and foliar spraying of MLE three or two times, respectively gave the maximum records for all studied parameters, with the lowest nitrate (NO3) content in edible head lettuce in two seasons. Regarding the mentioned results, it could be recommended that foliar application of head lettuce plants twice with EM at 5 cm3/l combined with three times sprayings of MLE are promised for enhancement of head lettuce (cv. Big bell) productivity and quality under Dakahlia Governorate conditions.