A cellular feature of Parkinson's disease is cytosolic accumulation and amyloid formation of α‐synuclein (α‐syn), implicating a misregulation or impairment of protein degradation pathways that involve the proteasome and lysosome. Within lysosomes, Cathepsin (Cat) D, an aspartyl protease is suggested to be responsible for α‐syn clearance; however, the protease alone only generates amyloidogenic C‐terminal truncated species (e.g. 1–94 and 5–94), arguing that other proteases and/or environmental factors within the lysosome are needed to facilitate degradation and to avoid α‐syn aggregation. Here, we show that in addition to aspartyl cathepsin activity, purified mouse brain and liver lysosomes harbor cysteine cathepsin activity identified as Cat B and L by using liquid chromatography mass spectrometry and peptide mapping. In contrast to Cat D, both Cat B and L cleave α‐syn within its amyloidogenic region (residues 20–100) generating short peptides that are not aggregation prone. Surprisingly, we discovered that Cat L is efficient in degrading α‐syn amyloid fibrils, which by definition are resistant to broad spectrum proteases. Based on these results, stimulating Cat L activity or increasing its level is a potential strategy for clearance of aggregated α‐syn in lysosomes.