Bactrocera zonata (Saunders) (Diptera: Tephritidae) is an important insect pest of fruits in Egypt. The desire for fresh fruits free of insecticides drives the adoption of environmentally friendly biopesticides to manage pests. The current study sought to estimate the toxicity and biochemical alterations of 3rd larval instar of B. zonata affected by clove, neemazal T/S, garlic, ginger and orange oils compared with indoxacarb at LC50 under laboratory conditions. Results after 24 h of treatment indicated that neemazal T/S is more toxic than other tested oils compared with higher toxicity of indoxacarb with LC50 values of 86.09, 174.72, 4514.38, 7224.01, 9387.73 and 2590.2 μg/mL for indoxacarb, neemazal T/S, ginger, clove, garlic and orange oils, respectively. Moreover, after 24 h of treatment, the larval content of digestive enzymes drastically decreased. All compounds caused a remarkable reduction in protease (except clove oil), aspartate aminotransferase (AST), alanine aminotransferase (ALT), phenol oxidase enzyme, α-esterase (except indoxacarb and neemazal T/S) and β-esterase (except ginger oil and neemazal T/S) activity. Also, total carbohydrates, total lipids and total proteins take the same trend. All treatments at LC50 increased the activity of cytochrome p450 and glutathione-s-transferase against 3rd larval instar of B. zonata compared with control. Our findings recommended that the tested botanicals could be an effective substitute for conventional insecticides as well as their safety for human beings and beneficial organisms.