Rhizoma coptidis (RC) has been used as an herbal medicine in China for over one thousand years, and it was subjected to specific processing before use as materia medica. Processing is a pharmaceutical technique that aims to enhance the efficacy and/or reduce the toxicity of crude drugs according to traditional Chinese medicine theory. In this study, the chemical profiles of RC, ginger juice processed RC (GRC), and water processed RC (WRC) was determined to reveal the mechanism of processing of RC. UPLC-QTOF-MS analysis of methanol extract of RC, GRC, and WRC has been conducted to investigate the effect of processing on the composition of RC. HPLC-PDA was used to determine the variance of total alkaloids and seven alkaloids of RC during the processing. The volatiles of RC, GRC and ginger juice were separated by distillation, the change of volatiles content was recorded and analyzed, and the qualitative analysis of the volatiles was carried out using GC-MS. The microstructures of RC, GRC and WRC were observed using a light microscope. Results showed that ginger juice/water processing had limited influence on the composition of RC’s methanol extract, but significant influence on the content of some alkaloids in RC. Ginger juice processing significantly increased (p < 0.05) the volatiles content of RC and changed the volatiles composition obviously. Processing also had an influence on the microstructure of RC. This research comprehensively revealed the mechanism of ginger juice processing of RC.