Abstract: Naturally−occurring serpentine Mg₃Si₂O₅(OH)₄, as one of the typical magnesium−rich layered clay minerals, is widely distributed in nature and has good industrial application prospects. However, the reactivity of natural serpentine is commonly low due to its stable crystal structure, which requires certain pre−treatment methods to increase the reactivity of serpentine to improve its utilization efficiency. Therefore, taking natural serpentine as an object, this paper employed ball−milling method to pretreat serpentine, and systematically investigated the effectiveness and mechanism of mechanochemical activation on its crystal structure and reactivity using XRD, FTIR, TG−DSC and SEM analytical techniques. Characterization results indicated that mechanochemical activation could induce serious deformation of octahedral structure within serpentine crystal and the rupture of a large number of Mg−O(H) bonds, gradually turning serpentine crystals to be amorphous state as the milling time increased. The solubility of serpentine in water and the fixation efficiency for heavy metal ions by activated serpentine were also measured. The results showed that after activation at 600 r/min for 5 min, the dissolution of 0.05 g serpentine in 100 mL water rapidly increased the solution pH to 9.98. The solution pH further increased to 10.45 as the ball−milling time extended to 60 min, with a Mg²⁺ dissolution concentration of activated serpentine approximately 11 times that of raw serpentine. Moreover, when the dosage of activated serpentine for 60 min was 0.5 g/L, the initial concentration of heavy metal ions was 100 mg/L, and the reaction time was 120 min, all the removal rate of Cu²⁺, Pb²⁺, Fe²⁺ and Ni²⁺ ions were greater than 95%, and the adsorption capacity of Cd²⁺ and Mn²⁺ ions reached to nearly 50 mg/g, which were much higher than the efficiency of heavy metal removal by thermally−activated serpentine under the same experimental conditions, reflecting the advantages of the lattice activation and reactivity improvement of serpentine based on mechanochemical activation. Mechanochemically activated serpentine could be potentially applied to the preparation of clay mineral−based functional materials and treatment of heavy metal pollution, promoting the coordinated development of resources and environment. In general, these obtained findings may provide certain technical supports for the mechanochemical activation of layered clay minerals such as serpentine and their applications as well.