Methamphetamine (METH) and ketamine (KET) are widely detected in surface waters and thus may pose threat to aquatic organisms. However, their degradation in aquatic systems and the effects on bacterial community were unknown. The present study investigated the biodegradation process of METH and KET in river waters and sediments. Three microcosms were examined over 40-days' incubation under (i) aerobic and illumination conditions, (ii) anaerobic condition exposed to light, (iii) anaerobic-dark condition. Statistically significant biodegradation of METH and KET (1 mg L-1) was observed in all treatments. The half-lives under the examined conditions indicate that the two drugs were refractory in aquatic environment. Moreover, there were no pronounced absorption and photolysis observed in this work. Illumina MiSeq sequencing analysis revealed that Methylophilaceae, Saprospiraceae, WCHBI-69, Desulfobulbaceae, Porphyromonadaceae, FamilyXI, Peptococcaceae, and Rhizobiaceae were the predominant candidatus families during KET and METH biodegradation, and the preponderance would impair other microorganisms' prosperity since them were scarcely detected in the wild. Meanwhile, canonical correlation analysis (CCA) indicates that METH as an environmental factor may affect bacterial community structure in field water samples.