Addition of suboptimum protein and higher lipid in the diet can be a better strategy to develop an environment friendly feed for cultured species. But very high amount of dietary lipids can cause metabolic burden to the species leading to growth retardation and lipid accumulation in the body of the animals. In this context, a feeding trial of 60 days was conducted to find out the effect of L-carnitine supplemented diets with different protein and lipid levels on growth, feed conversion, nutrient utilization, body composition, antioxidant status and physio-metabolic responses of Penaeus vannamei juveniles reared in inland saline water (ISW) of 10 ppt salinity. Three hetero-nitrogenous (36.17, 33.13, 30.11% crude protein, CP), hetero-lipidic (5.12, 8.15, 11.17% lipid) and hetero-caloric (378–411 Kcal digestible energy or DE/100 g) diets were supplemented with three levels (0%, 0.05% and 0.1%) of L-carnitine to prepare nine experimental diets viz. P36L5C0 (36% CP, 5% lipid and 0% L-carnitine), P36L5C0.05 (36% CP, 5% lipid and 0.05% L-carnitine), P36L5C0.1 (36% CP, 5% lipid and 0.1% L-carnitine), P33L8C0 (33% CP, 8% lipid and 0% L-carnitine), P33L8C0.05 (33% CP, 8% lipid and 0.05% L-carnitine), P35L8C0.1 (33% CP, 8% lipid and 0.1% L-carnitine), P30L11C0 (30% CP, 11% lipid and 0% L-carnitine), P30L11C0.05 (30% CP, 11% lipid and 0.05% L-carnitine) and P30L11C0.1 (30% CP, 11% lipid and 0.1% L-carnitine). Six hundred and seventy-five (675) acclimated P. vannamei juveniles (average body weight, 4.02 ± 0.01 g) were randomly distributed to nine treatments viz. P36L5C0, P36L5C0.05, P36L5C0.1, P33L8C0, P33L8C0.05, P33L8C0.1, P30L11C0, P30L11C0.05 and P30L11C0.1in triplicate following 3 (protein-lipid levels) × 3 (dietary levels of L-carnitine) factorial design. The shrimp fed with 33% protein, 8% lipid and 0.05% L-carnitine showed significantly (p < 0.05) the highest weight gain percentage, specific growth rate, protein efficiency ratio, lipid efficiency ratio, and protease activity and the lowest feed conversion ratio. The hepatopancreas somatic index (HPSI) value, whole body lipid content and activities of amylase and lipase significantly (p < 0.05) increased with increase in dietary lipid level with the highest values found in 11% lipid fed group, but dietary L-carnitine caused the decreasing trend of HPSI and increasing trend of lipase respectively with the lowest and the highest values in 0.05% L-carnitine fed group. Similarly, the 0.05% L-carnitine fed group showed significantly higher body lipid content and amylase activity than its non-supplemented counterpart. Body moisture content significantly decreased with increase in dietary lipid level with the lowest value in 11% lipid fed group. However, dietary L-carnitine did not affect the body moisture level. The 33% protein, 8% lipid and 0.05% L-carnitine fed group exhibited significantly higher Carnitine palmitoyl transferase-I and glucose-6-phosphate-dehydrogenase activity than non-supplemented groups. The shrimp of 11% lipid fed group showed significantly lowest serum total protein and the highest serum glucose, cholesterol and triglycerides, gill and hepatopancreatic superoxide dismutase (SOD) and catalase (CAT) and hepatopancreatic malondialdehyde (MDA). But, 0.05% L-carnitine fed group showed significantly higher serum total protein and lower serum glucose, cholesterol and triglycerides and lower tissue SOD, CAT and MDA. In conclusion, P. vannamei juveniles reared in 10 ppt ISW and fed with 33% crude protein, 8% lipid and 0.05% L-carnitine diet can exhibit better growth performance, body lipid content, antioxidant status and physio-metabolic responses. This information will be useful in formulating the L-carnitine supplemented eco-friendly low protein high lipid or energy (LPHL or LPHE) feed for profitable culture of P. vannamei in ISW.