Background: Panax ginseng is a perennial medicinal herb also known as Korean ginseng or Insam (인삼), commonly found in Korean Peninsula. These herbs are used to treat different types of diseases. Recent studies have shown that phytochemicals found in P. ginseng harbor anticancer activity against various cancers. However, the biological and molecular mechanisms of these phytochemicals are still unknown in osteosarcoma (OS). Materials and Methods: This study utilized the network pharmacology method comprised target prediction, gene enrichment and ontology, KEGG pathway analysis, and gene expression studies. The obtained results were used to predict the interaction of phytochemicals with the human CDKL3 domain implicated in OS using molecular docking. Toxicity and pharmacokinetic elements of these phytochemicals were also identified. Results: Results showed that Fumarine and Inermin are bioactive phytochemicals that have a multimodal effect on multiple targets and pathways involved in the progression of OS. These compounds were able to regulate the expression of genes and interacted with human CDKL3. These compounds have good pharmacokinetic and toxicological characteristics. However, they exert a high risk of hepatotoxicity. Conclusion: The present study provided a predicted mechanism of action of bioactive phytochemicals of P. ginseng in the inhibition of OS.