Nickel is an important raw metal material in industry, which has been identified as a strategic mineral resource by the Chinese Ministry of Land and Resources. Nickel sulfide ore accounts for 40% of all nickel ores worldwide. However, magnesium silicate gangue minerals in sulfide nickel ores, particularly serpentine, pose significant challenges to the flotation of nickel sulfide ores. The presence of magnesium silicate gangue leads to a series of issues, including increased energy consumption in subsequent smelting processes, accelerated equipment wastage, and increased SO2 emissions, which severely impact the comprehensive utilization of nickel resources in sulfide nickel ores. In this regard, flotation depressants are the most direct and effective method to reduce adverse influences caused by magnesium silicate gangue in the flotation of nickel sulfide ore concentrate. Based on the characteristics of the typical magnesium-containing nickel sulfide ore, this review illustrates the difficulties of the depression of magnesium silicate gangue during the flotation of nickel sulfide ore and gives an overview of the common depressants from six aspects (chelation depressants, dispersion depressants, flocculation depressants, depressants for grinding, depressants for slurry adjustment and combination depressants). Each section summarizes the relevant depression mechanisms and analyzes the advantages and disadvantages of various reagents, providing a reference for designing depressants specifically targeting serpentine.