The HIV-negative factor (Nef) protein is an accessory pathological component that plays a crucial role in the condition known as acquired immune deficiency syndrome (AIDS). The HIV virus which lacks Nef took time to transformed into AIDS. As a consequence, attacking the Nef molecule is viewed as a significant strategy for HIV/AIDS treatment. Only a few drugs have been discovered as Nef inhibitors until date. The present effort seeks to find putative HIV-1 NEF antagonists among a collection of plant compounds. Following ADME assessment, among the one hundred, twenty phytocompounds that were docked in conjunction with HIV-1 NEF to determine their inhibitory effectiveness with respect to the NEF Protein. Ten of the 20 compounds have strong binding affinity. Then, only six of the 10 substances succeeded the tests for toxicity (mutagenicity). These antagonists' reactivity was studied. According to the outcomes of the Molecular dynamic simulations, the affinity of these inhibitors was high in relation to other compounds. These results imply that the selected botanical compounds offer promising treatments to combat HIV in future.