During the last few decades, the increase in the incidence of multidrug-resistant (MDR) fungal infections has become an emerging threat to public health. Therefore, it is important to illuminate the usage of alternative therapy to treat MDR fungal infection. This study was carried out to elucidate the usage of plant extract and essential oil, either alone or with other antifungal drugs to treat otitis media caused by MDR fungi. Medicinal plant is a safe and cheap source when compared with chemical antifungal drugs. Twenty-one fungal isolates out of 104 ear swabs from patients suffering from otitis media were characterized using both phenotypic and genotypic methods. The antibiogram typing was used to determine the MDR isolates. The sensitivity of MDR fungal isolates was tested against several plant extracts and essential oils, either alone or with other antifungal drugs. Thyme oil and clove extracts proved to have synergistic effects suggesting their use in the treatment of fungal infections, especially otitis media caused by MDR fungi. The ultrastructure of MDR fungal isolates exhibited a complete destruction post exposure to the used materials when observed under the transmission microscope (TEM). Thyme oil and clove extract were found to be the most effective agents against MDR fungal isolates and they constitute a promising tool for the management of fungal infection causing the otitis media.