For millennia, plants have been integral to medicinal practices, with garlic (Allium sativum) valued for its bioactive compounds like flavonoids and organosulphur derivatives. While garlic bulbs are well-studied, the flavonoid-rich fraction of garlic skin (FRFGS), typically discarded as agricultural waste, remains underexplored. This study evaluates the phytochemical composition and safety profile of FRFGS through acute and 28-day sub-acute toxicity studies in Wistar rats. FT-IR and GC-MS analyses identified flavonoids, fatty acids (e.g., palmitic and stearic acids), and hydrocarbons, contributing to antioxidant, antimicrobial, and anti-inflammatory properties. Acute toxicity tests using Economic Cooperation and Development (OECD) guideline 423 at 300 and 2000 mg/kg body weight of FRFGS revealed no mortality or behavioural changes, but histopathological analysis showed dose-dependent liver, kidney, and heart damage at higher doses. The 28-day sub-acute study confirmed safety at lower doses (500 and 1000 mg/kg body weight of FRFGS), with no significant alterations in behaviour, food, or water intake. However, higher doses (2000 mg/kg body weight of FRFGS) induced lower body weight gain, elevated liver and kidney function markers, and histopathological changes in these organs, indicating potential stress or mild damage. Haematological parameters were largely unaffected, except for a slight increase in mean corpuscular volume and a dose-dependent reduction in platelet count (p<0.05), suggesting minimal impact on blood health. These results show the need for caution at larger doses but also establish the promise of FRFGS as a source of bioactive chemicals for use in pharmaceutical, nutraceutical, or functional food applications.