The objective of this research was to investigate the effects of Zn²⁺- and Cr³⁺-modified palygorskite (ZCM-Pal) in an experimental E. tenella infection in chickens. ZCM-Pal was produced by cationic ion exchange with Zn²⁺/Cr³⁺ and palygorskite (Pal). The anticoccidial activity of ZCM-Pal, Diclazuril was evaluated by comparing the differences in the anticoccidial index (ACI). During the experiment, clinical signs, bloody feces, relative weight gain (RWG), survival rate (SR), cecal lesion scores (LS), and oocysts/gram of feces (OPG) were recorded in all the chickens to calculate the ACI. The results showed that the ACI of the ZCM-Pal group (10 g/kg) was 170.38, indicating moderate activity. The histopathological examination of cecal samples revealed that the ceca from the chickens medicated with ZCM-Pal were intact compared with those from chickens from the infected control. The number of inflammatory infiltrates and parasites in ZCM-Pal group was less than the other groups. The blood endotoxin concentrations were decreased with supplementation of ZCM-Pal. At the end of the experimental period, the weight gain of chickens treated with ZCM-Pal was similar to those in the uninfected control group. These results suggested that ZCM-Pal might be an aid in the control of E. tenella in chickens.