Plastic pollution represents a persistent global issue, with catastrophic effects on ecosystems. Due to unique properties, these synthetic materials do not break down into biodegradable compounds when naturally dispersed, but degrade into smaller fragments, known as micro- (MPs) and nanoplastics (NPs), that easily enter the food chain. Among plastics, polypropylene (PP) is one of the most common, whose consumption has dramatically increased in recent years for single-use packaging and surgical masks. In this context, given the widespread detection of PP-MPs and NPs in various biological matrices, investigating their toxicity in living organisms is crucial. For these reasons, this study aims to assess how PP-MPs and NPs affect tissue regeneration following injury, proposing the freshwater leech Hirudo verbana as an established experimental model. Injured leeches were examined at different time points after plastic administration, and analyses were conducted using microscopy, immunofluorescence, and molecular biology techniques. The results demonstrate that plastic exposure induces fibrosis, disrupts tissue reorganization, delays wound repair, and activates the innate immune and oxidative stress responses. In summary, this project provides new insight into the adverse effects of PP particles on living organisms, highlighting for the first time their negative impact on proper tissue regeneration.