The foot and mouth disease (FMD) vaccine is used to control the FMD in cloven-hoofed animals including calves. The most important step in vaccine preparation is the selection of a suitable adjuvant which plays a main role in the vaccine’s potency. The present study is an attempt to use clinoptilolite instead of Montanide oil to enhance the efficiency of the FMD vaccine and reduce its production cost. Twelve calves were split into four groups. Three groups were vaccinated with FMD vaccine with different adjuvants i.e. 100% Montanide (ISA 206), 50% of Montanide with 1.0 μg/dose of clinoptilolite (ISA 206+CLINP), and by replacing the 100% of Montanide to 1μg/dose of clinoptilolite (CLINP). The fourth group was unvaccinated. Results showed that calves vaccinated with (ISA 206+CLINP) FMD vaccine expressed the highest and the longest periods of immune response until 38 weeks. While groups vaccinated with (CLINP) or (ISA 206) vaccine showed only protection up to 26 and 34 weeks respectively. Also, our results showed that clinoptilolite improved organ functions resulting from the stress of vaccines. Finally, this study recommended the use of clinoptilolite with Montanide oil as a potential adjuvant in the FMD vaccine to give high stimulation of the immune response.