3-Tetrazolyl-β-carbolines were prepared by the Pictet-Spengler approach using a tryptophan analogue as building block, in which the carboxylic acid was replaced by the bioisosteric tetrazole group. Knowing that β-carbolines are often associated with psychopharmacological effects, the study of the 3-tetrazolyl-β-carbolines as potential neuroprotective agents against Parkinson's disease was investigated. The evaluation of neuroprotective effects against 1-methyl-4-phenylpyridin-1-ium (MPP + )-induced cytotoxicity allowed to identify compounds with relevant neuroprotective activity. One derivative, 3-(1-benzyl-1H-tetrazol-5-yl)-1-(p-dimethylaminophenyl)-β-carboline, stood out for its low cytotoxicity and excellent performance, preventing cell death induced by this neurotoxin. The most promising compounds were also evaluated for their neuroprotective properties against iron (III)-induced cytotoxicity. However, only one 3-tetrazolyl-β-carboline derivative slightly reduced iron-induced cytotoxicity. Overall, the neuroprotective properties of 3-tetrazolyl-β-carbolines have been demonstrated and this finding may contribute to the development of new therapies for Parkinson's disease.