The development of antimicrobial drugs has become essential due to the increasing resistance among microorganisms, largely driven by the indiscriminate use of antibiotics. Similarly, the misuse of antifungal agents over recent decades has contributed to the emergence of numerous drug-resistant fungal strains. The World Health Organization (WHO) recognizes antibiotic resistance as one of the top ten global public health threats. Infections caused by multidrug-resistant microorganisms are steadily rising, presenting a major challenge in modern medicine. Alkaloids represent one of the largest classes of natural compounds. These plant-derived chemicals play a defensive role, protecting plants against microorganisms, herbivores, and pests. Many alkaloids exhibit diverse biological activities, and some have been successfully developed into therapeutic agents with various pharmacological properties. This review explores a wide spectrum of plant-derived alkaloids with potential antifungal activity. Notable alkaloid classes include pyridines, quinolizidines, indoles, tropanes, piperidines, purines, imidazoles, and isoquinolines. These compounds can inhibit the growth and activity of various fungal species. While previous reviews have mentioned the general biological activity of natural and synthetic alkaloids, few have provided an in-depth analysis of their antifungal mechanisms. In this review, we discuss several primary antifungal mechanisms, including inhibition of fungal cell wall synthesis, disruption of cell membrane permeability, interference with fungal metabolism, and suppression of nucleic acid and protein synthesis. Our findings highlight that plant-derived alkaloids play a significant role in combating fungal pathogens, including drug-resistant strains. Therefore, alkaloids hold promising potential as effective agents against multidrug-resistant fungi. This review aims to address the urgent issue of antifungal resistance and offer a scientific foundation for the development of novel antifungal therapies.