The purpose of this study was to demonstrate the neuroprotective effect of heat-treated fermented black beans. The production of fermented black beans was optimized using Lactiplantibacillus plantarum SMF470 and L. plantarum SMF796 strains isolated from kimchi as starters. Compared to heat-treated black bean extract, heat-treated fermented black beans showed significantly higher DPPH and ABTS radical scavenging activities, as well as higher total polyphenol content (p <0.05). The neuroprotective effect through the gut-brain axis was evaluated using conditioned medium (CM) obtained by culturing heat-treated fermented black beans in intestinal cells (HT-29). The CMs of heat-treated fermented black beans from SMF470 and SMF796 showed a high protective effect on SH-SY5Y human neuroblastoma cells induced by oxidative stress from H2O2. Additionally, the CMs of heat-treated fermented black beans were found to protect SH-SY5Y cells from toxicity induced by MPP+. SMF470-CM and SMF796-CM significantly increased the expression of brain-derived neurotrophic factor (BDNF) in SH-SY5Y cells treated with MPP+, while lowering the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (p <0.05). Furthermore, SMF470-CM and SMF796-CM lowered the apoptosis-related Bax/Bcl-2 ratio. The results of this study suggest that heat-treated fermented black beans can be utilized as potential health functional materials for the prevention and improvement of degenerative brain diseases.