The main objective of present study was to evaluate the toxicity of Malathion 57% EC, Potegon 20% SP, K.Z oil, and Neem (Azadirachta indica) extract AgNPs for controlling the cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae) and their effects on enzymes as indicators on soil fertility in tomato plants (Lycopersicum esculentum). The tested insecticides could be arranged in descending order according to their potency as follows: Malathion 57% EC > Potegon 20% SP > K.Z oil > Neem extract AgNPs. These compounds succeeded in controlling A. gossypii, where the means of reduction percentages of infestation were 79.92, 72.61, 73.18 and 72.52 %, respectively in the 2018/2019 season opposed to 76.09, 74.61, 72.97 and 71.38 %, respectively in the 2019/2020 season. The enzymes activity were not affected by the K. Z. oil, and Neem extract AgNPs applied on tomato plants. Mineral oil and plant extracts could form the basis for a successful formulation of bio-pesticides.