My study explores the potential anticancer properties of primarily two natural small molecule compounds, diosgenin and panaxadiol, in relation to Retinoic Acid Receptor-related Orphan Receptor Gamma (RORγ)-mediated cancer pathways. RORγ, a nuclear receptor, has been identified as a significant player in various cancers, and its inhibition has emerged as a promising therapeutic strategy. The compounds diosgenin, derived from fenugreek, and panaxadiol, isolated from the Panax genus, have shown promising anticancer activity in various pre-clinical models. However, their activities against RORγ in cancers remain unexplored. Through in-vitro experiments and RNA-seq-based functional analysis, my research investigated the effects of diosgenin and panaxadiol on RORγ-mediated signaling pathways and tumorigenesis. My findings suggest a significant inhibition of cancer cell proliferation in triple-negative breast cancer (TNBC), prostate and lung cancer cell models upon treatment with these compounds. Furthermore, RNA-seq analysis indicated that RORγ-mediated biochemical pathways such as cholesterol biosynthesis and metabolism are enriched in the differential gene expression profiles from the cells treated by the compounds. These preliminary results, therefore, suggest that diosgenin and panaxadiol could serve as novel therapeutic agents in the management of RORγ-related cancers. Further research is warranted to fully elucidate their anticancer mechanisms, potential synergies with existing therapies, and their efficacy in clinical trials. This research provides a critical step forward in the ongoing search for more effective and targeted therapies in the treatment of complex malignancies.