Introduction of finely disperse mineral additives of natural and man-made origin to Portland cement in order to improve the indicators of its physical-mechanical properties and partially replace clinker is one of the urgent directions for solving the resource and energy saving problems, as well as environmental protection problems in the production and application of building materials. The expansion of the raw material base of mineral additives can be achieved by using calcined polymineral clays, which are common in many regions of the Russian Federation, including the Republic of Mordovia. The article presents the results of research on the effects of calcination temperature and time of thermally activated polymineral clays of the Republic of Mordovia on their physical-chemical efficiency in cement systems. According to the study results of dehydration processes of clay minerals using the synchronous thermal analysis, it is established that the optimum calcination temperature for clays of Nikitsky and Staroshaigovsky deposits located in the area of 500–800 °C. This temperature range corresponds to the processes of the initial crystal structure restructuring of clay minerals of the kaolinite and illite groups, associated with their dehydroxylation, which contributes to the transition of these phases to the active form. The optimization of calcination parameters of polymineral clays based on the study results of influence of their additives on the mixed cement binder activity confirmed the thermal analysis data. It was found that the production of mineral additives with the highest values of the activity index is facilitated by 2-hour heat treatment of clays at 700 °C. At the specified calcination parameters, the replacement of 10% of Portland cement with the additive of thermally activated Nikitsky clay allows achieving the mixed binder activity that exceeds by 3 % the same indicator of mixed binder based on Portland cement and high-quality metakaolin.