Human phospholipase A₂ (hPLA₂) of the IIA group (HGIIA) catalyzes the hydrolysis of membrane phospholipids, producing arachidonic acid and originating potent inflammatory mediators. Therefore, molecules that can inhibit this enzyme are a source of potential anti-inflammatory drugs, with different action mechanisms of known anti-inflammatory agents. For the study and development of new anti-inflammatory drugs with this action mechanism, snake venom PLA₂ (svPLA₂) can be employed, since the svPLA₂ has high similarity with the human PLA₂ HGIIA. Despite the high similarity between these secretory PLA₂s_, it is still not clear if these toxins can really be employed as an experimental model to predict the interactions that occur with the human PLA₂ HGIIA and its inhibitors. Thus, the present study aims to compare and evaluate, by means of theoretical calculations, docking and molecular dynamics simulations, as well as experimental studies, the interactions of human PLA₂ HGIIA and two svPLA₂s_, Bothrops toxin II and Crotoxin B (BthTX-II and CB, respectively). Our theoretical findings corroborate experimental data and point out that the human PLA₂ HGIIA and svPLA₂ BthTX-II lead to similar interactions with the studied compounds. From our results, the svPLA₂ BthTX-II can be used as an experimental model for the development of anti-inflammatory drugs for therapy in humans.