Coffee is one of the most popular and consumed products in the world, generating tons of solid waste known as spent coffee grounds (SCG), containing several bioactive compounds. Here, the antifungal activity of ethanolic SCG extract from caffeinated and decaffeinated coffee capsules was evaluated against yeasts and filamentous fungi. These extracts had antifungal activity against Candida krusei, Candida parapsilosis, Trichophyton mentagrophytes, and Trichophyton rubrum, all skin fungal agents. Moreover, SCG had fungicidal activity against T. mentagrophytes and T. rubrum. To understand the underlying mechanisms of the antifungal activity, fungal cell membrane and cell wall components were quantified. SCG caused a significant reduction of the ergosterol, chitin, and β-(1,3)-glucan content of C. parapsilosis, revealing the synthesis of this membrane component and cell wall components as possible targets of these extracts. These extracts were cytotoxic for the tumoral cell lines tested but not for the non-tumoral PLP2 cell line. The analysis of the phenolic compounds of these extracts revealed the presence of caffeoylquinic acid, feruloylquinic acid, and caffeoylshikimic acid derivatives. Overall, this confirmed the antifungal activity of spent coffee grounds, presenting a potential increase in the sustainability of the life cycle of coffee grounds, as a source for the development of novel antifungal formulations, especially for skin or mucosal fungal infections.