Abstract Aim The intractable, mucormycosis, caused by Mucorales primarily targets immunocompromised individuals. The first-line therapy, intravenous liposomal amphotericin B and surgical debridement of necrotic tissue, is contraindicative in individuals with compromised kidneys. This invokes a pressing need to identify safer treatment options. Methods and Results The antifungal effect of the classical nasal drop, Anu taila, against Mucor spp. was investigated through microbiological, cytological, analytical chemical (HPLC and GS–MS/MS) and scanning electron microscopic (SEM) approaches. Anu taila-pretreated spores germinated late, resulting in reduced infectivity, observed as milder monocytic immune response. Conversely, Anu taila-pretreated human THP-1 cells exhibited an improved immune response against Mucor spores, through TNF-α. Repeated Anu taila application rapidly abolished fungal microarchitectures than amphotericin B, evident from swift replacement of hyphae, sporangiophores and sporangia with fused biomass, in the SEM images. HPLC analysis showed that Anu taila treatment significantly reduced overall ergosterol content in Mucor biomass. Anu taila also downregulated sterol-C5-desaturase-coding ERG3 gene, crucial for ergosterol biosynthesis and resultant structural integrity, in Mucor spp. Conclusion Taken together, Anu taila was found effective against Mucor spp., with both prophylactic and curative implications, which is attributable to the phytochemical composition of this classical nasal drop. Significance and Impact Statement The potential remedial effects of a classical nasal drop against an obdurate and challenging fungal infection are identified.