Rhodamine B (RhB), widely used as an industrial dye, is a toxic organic that is hazardous to human health and can cause water pollution. In this study, the removal rate of RhB was investigated by the following methods: hydrodynamic cavitation (HC) operated individually, and HC combined with oxidants H2O2 or ClO2. The effect of different operating parameters including pressure (2–6 bar) and initial pH (2–8) on the extent of degradation was investigated using an orifice plate as the cavitation device to achieve maximum removal of RhB. Under the parameters of HC, the effect of different loadings was investigated: H2O2 (n(RhB):n(H2O2) was varied from 1:17.60 to 1:211.28) and ClO2 (n(RhB):n(ClO2) was varied from 1:8.87 to 1:177.53). A combination of cavitation and H2O2 or ClO2 resulted in degradations of 80.6% and 95.3%. The results indicated that the combination of HC and oxidants was better than the individual HC process for the degradation of RhB. When combining HC with H2O2 or ClO2, the synergistic coefficients of 62.54 and 74.79 were obtained. The combination of HC and ClO2 was proven to be more effective for the removal of RhB compared to HC alone and the hybrid process of HC and H2O2.