Background: The increasing azole-resistance among Candida albicans isolates worldwide justifies the search for newer antifungal natural agents, such as garlic. This study aimed to explorethe antifungal and antibiofilm activity of garlic extract on Candida albicans, and the associated polymorphism of protein bands. Results were compared to fluconazole. The minimum inhibitory concentration (MIC) of garlic extract and fluconazole was done for 19 C. albicans clinicalisolates using the micro broth dilution method. The antibiofilm activities of garlic and fluconazole were studied, and the minimum biofilm inhibitory and eradication concentrations (MBIC and MBEC, respectively) were measured. C. albicans protein expression patterns were assessed using protein electrophoresis. Results: Garlic had a better inhibitory effect on planktonic cells (lower MICs) compared to fluconazole (94.4% versus 77.7%, respectively). In contrast, fluconazole had a better anti-biofilm activity compared to garlic (88.9% and 72.2%, respectively). Garlic inhibited and eradicated the formation of biofilm in 72.2% and 61.1% of samples, respectively, while 88.9% of isolates were equally inhibited and eradicated by fluconazole. The median number of protein bands of untreated planktonic isolates was nine bands, while garlic-treated and fluconazole-treated planktonic isolates produced significantly more bands [median of 16 bands (p < /em>< 0.001) and 14 bands (p < /em>= 0.003), respectively]. Conclusions:  The proteomic changes associated with antifungal activity caused by garlic exposure highlight its potential role as a natural antifungal and anti-biofilm agent. Paradoxical regrowth of cells suggests a fungistatic rather than fungicidal activity.