Manganese sulfate is present in nature as numerous mineral forms such as, jokokuite, pentahydrite, szmikite, and mallardite. Manganese is found in various superoxide dismutases.

Manganese (II) sulfate monohydrate has been used as a micronutrient for preparation of nutritive medium for growth of sugarcane plantlets. It has also been used as a trace element in the preparation of N6 complete nutrient liquid medium for growing mycelia of H. cylindrosporum.

Manganese(II) sulfate monohydrate is plant cell culture tested (0.6 g/ml) and is appropriate for use in plant cell culture experiments. Manganese (II) sulfate is a component of several plant cell culture media including: Chu′s N6; DKW/Juglans; Murashige and Skoog; and Gamborg′s B-5 media.

Manganese sulfate has various industrial applications such as dyeing, porcelain glazing, and the manufacture of fertilizers and boiling oils. MnSO₄ is used as a source of manganese ion in biological research, such as in culturing of Bacillus licheniformis and the induction of chromosomal abnormalities in plants. MnSO₄ has been utilized to investigate the enzyme dependent glycosylation of endogenous glycoproteins in human skeletal muscle.