This study demonstrated the use of nesquehonite (MgCO3×3 H2O) in producing plasterboard. Nesquehonite (NQ) can be activated via thermal treatment under 50–175°C, after which the dehydrated nesquehonite can hydrate to form a plaster-like product, like gypsum-based plaster. Here, we developed different blends of NQ and hemihydrate (dehydrated gypsum) to produce plaster. In addition, the influence of trace elements (i.e., sulfate and ammonium) on the reaction kinetics, mechanical properties, microstructure, phase assemblage, and evolution of the developed plasters were investigated. The target was to achieve comparable manufacturing process and compressive strength with the conventional gypsum plaster process using NQ as a major precursor. Data revealed that the mixes containing 75 % NQ obtained from 2 different synthesis routes (i.e., wet carbonation or chemically-synthesis route) attained 6–8 MPa compressive strength after 28 days of curing, which was comparable to those observed in gypsum-based products. The chemically synthesized NQ achieved the stability of NQ in the plasterboard sample, while the use of wet-carbonated NQ led to the formation of dypingite. Furthermore, the water resistance of plasterboard mixes with 100 % NQ outperformed that of gypsum, without any decline in compressive strength after water exposure.