Aim: In this study, the cytotoxic potential of the endemic Helianthemum germanicopolitanum Bornm. plant against colon cancer is investigated. Materials and Methods: This study pioneers the investigation of medicinal applications of the H. germanicopolitanum plant, specifically targeting the HT-29 human colon cancer cell line. The phytochemical profile of the aerial parts of the plant, especially the flavonoid content, was analyzed using High Performance Liquid Chromatography (HPLC). Cytotoxic effects were then evaluated by WST-1 assays on the HT-29 cell line; this revealed time- and dose-dependent inhibition of cancer cell growth. Results: These results also highlight the need for comprehensive research into H. germanicopolitanum's unique flavonoid composition and its broader implications in cancer treatment. Conclusion: These results also highlight the need for comprehensive research into H. germaicopolitanum's unique flavonoid composition and its broader effects in cancer treatment.