The valley of the Ouislane River (Meknes) undergoes anthropic pressure, which acts mainly on the river water quality. A study of the impacts of anthropogenic activities on the distribution and biodiversity of benthic macroinvertebrates and water quality of the Ouislane River was conducted. This study focused on five stations: from the source to the exit of the city of Meknes, with a monthly sampling frequency in 2010. We analyzed twelve physicochemical parameters and determined the diversity (Shannon-Wiener and Evenness Index) as well as the biological index through the benthic macroinvertebrates, based on the SEQ-V.2 scoring system. The relationships between the physicochemical and the macrobenthic data were investigated by biotypology analysis (PCA and FCA) and Pearson correlation analysis. According to the SEQ-Eau, The results obtained show that the water quality in station (O1) is of good quality, but the ecological functioning of the river is very disturbed ‘‘polluted’’ when it passes through the agglomeration of Meknes (O2). Downstream, the water quality is average in the O4-O5 section. Four variables are involved actively in the individualization of the physico-chemical environment: COD, dissolved oxygen, TSS and BOD5. The total number of macrobenthic taxa and their overall richness indices and diversity indices were significantly higher at the station (O1) than other stations. The analyses showed that the richness and diversity indices were generally influenced by the total suspended solids, chemical oxygen demand and biology oxygen demand of the river water. This study also highlighted the impacts of anthropogenic activities on the distribution and species diversity of macrobenthic invertebrate. Some sensitive (Trichoptera) and resistant species (Tubifex sp.) are identified as potential bioindicators of river ecosystems. The data obtained in this study supported the use of the bioindicator concept (Innovative Biotechniques for biomonitoring water quality) for North Africa Rivers because it is more efficient than conventional methods.