A study was conducted to determine the kinetics of Fasciola gigantica infection induced antibody response against oxyclozanidelevamisole in naturally infected bovine of South Gujarat, India. Faecal analysis on before, 1st, 4th, 8th, 11th and 37th days post treatment (DPT) recorded 67.14, 34.29, 5.71, 0 and 0% parasites infected bovines. Either parasite(s) positive indigenous cattle or buffalo become parasite(s) free by 8th DPT but a lag period of 4 days had been recorded in the exotic cattle. The trematode parasites infected animals take more time to clear the infection with the used drugs, it’s become 100% negative on 11th DPT while the nematodes parasites infected animals successfully clear the infection by 4th DPT and maintain it until the end of experiment. The 5 animals which showed reactivity in dipstick ELISA test following natural infection with F. gigantica using parasites specifi c diagnostic antigen, cathepsin L cysteine proteinase (CP), was subjected to indirect plate ELISA assay, the mean anti-CP antibody titer was recorded at its maximum at pretreatment in treated group positive animal when probed with CP antigen. Thereafter, a declining trend of antibody response was recorded in these naturally infected bovines which reached to undetectable level on 90th DPT in response to anthelmintic therapy while untreated animals (negative and positive animals) showed almost similar pattern of antibody response during the experiment. A signifi cant decrease in % eosinophilia count was also observed at 37th DPT in response to treatment.