The extensive use of organic UV filters (OUVFs) has led to these compounds being ubiquitously detected in the environment and considered a new kind of environmental pollutant. As OUVFs cannot be efficiently eliminated by conventional treatment processes, there is an urgent need to develop new innovative solutions for their removal. The present work investigates the efficacy of three Cunninghamella strains in the biodegradation of OUVFs: oxybenzone (BP-3) and 3-(4-methylbenzylidene)camphor (4-MBC). Moreover, a cytochrome P450 (CYP450) inhibition study was conducted, and Cunninghamella-processed samples in silico and in vitro toxicity were evaluated. Our results indicated the ability of Cunninghamella strains to utilize OUVFs. Among the tested Cunninghamella strains, both agents were the most efficiently removed by C. blakesleeana. These results were comparable with A. niger biodegradation capacity. In vitro studies of the fungi-processed samples confirmed no mutagenicity in the Ames test and the lack of cytotoxicity against HepG2 cell line. Moreover, Cunninghamella treatment positively influenced OUVFs SH-SY5Y neurotoxicity and ecotoxicity. After fungal treatment, BP-3 agonistic estrogenic activity was higher, whereas antagonistic androgenic effect was lower than before biotransformation. 4-MBC, after biotransformation, lost agonistic estrogenic activity, but gained antagonistic estrogenic properties. Additionally, this study confirmed the involvement of CYP450 enzymes in BP-3 and 4-MBC biotransformation, thus contributing to a better understanding of the detoxification pathways of OUVFs in fungi. In conclusion, these findings demonstrated, for the first time, that using environmental fungi Cunninghamella for the biodegradation of BP-3 and 4-MBC represents a potent approach for eliminating contaminants from the natural environment.