Helminthic infection is an important health problem that affects millions of humans and animals, especially in developing countries. This study aims to research some natural compounds which can be used continuously in the treatment of recurrent helminthic infections. For this purpose, we predicted the anthelmintic properties of some bioactive compounds from Artemisia annua L., Momordica charantia L., Origanum vulgare subsp. hirtum, and Rubus canescens DC. These compounds were docked with anthelmintic target proteins; Hcβ-tubulin (Haemonchus contortus β-tubulin), AsFR (Ascaris suum fumarate reductase), and CPT 2 (rat carnitine palmitoyl transferase 2) enzyme using AutoDock 4.2 program. The chemical interactions and ADME properties of the most potent ligands were investigated via Biovia Discovery Studio Client 2020 and SwissADME. In the results, it was demonstrated, based on molecular interactions, that oreganol, momordicin II, cucurbitacin-B, and charantadiol-A have multi-inhibitory properties against target proteins. It was revealed for the first time that oreganol, cucurbitacin-B, charantadiol-A, and momordicin II inhibited CPT 2 and AsFR enzymes at nanomolar inhibition constants (0,137 nM, 0,0571 nM, 2,06 nM, and 0,072 nM for CPT 2 enzyme; 1,9 nM, 5,31 nM, 16,6 nM, and 40,78 nM for AsFR, respectively). Oreganol has also inhibited Hcβ-tubulin at low Ki values (Ki = 24,32 nM). These findings hold significant implications in the medical field, as they indicate that the compounds in question could serve as broad-spectrum anthelmintic drugs. When broad-spectrum drugs are needed, the oreganol scaffold can be used since it is triple-acting inhibitor. Cucurbitacin-B can be a candidate molecule to replace Ivermectin because they compete for the same target. According to the study’s findings, future anthelmintics may be developed from cucurbitacins, adding to the effective treatments already provided by benzimidazoles and macrocyclic lactones. This research represents the first instance in which essential in silico scientific data has been gathered to support this conclusion.