Inorganic mercury IHg is the major Hg species as well as the precursor of methylmercury, but few studies have investigated the toxicities of inorganic mercury in comparison to methylmercury in marine environments. In this study, the acute effects 24 h of IHg HgCl2 on the nervous system of M. chinensis philippi were investigated using metabolomics, calcium ions Ca2+, neurotransmitters nitric oxide, glutamate, acetylcholine and related enzymes calcineurin, nitric oxide synthase and acetylcholinesterase. In M. chinensis philippi of the Hg-treated group, decreased metabolites included alanine, glutamate, succinate and homarine increased metabolites included glutamine, inosine and glucose. The metabolic pathways affected mainly included glycolysis citrate cycle nucleotide metabolism alanine, aspartate and glutamate metabolism nucleotide metabolism and osmotic regulation. Compared to the control group, the levels of the neurotransmitters nitric oxide and acetylcholine in Hg-treated M. chinensis philippi were decreased, while glutamate increased significantly, the activity of nitric oxide synthase was increased, while acetylcholinesterase decreased significantly, and the activity of calcineurin had a statistically insignificant increasing tendency. The concentration of Ca2+ in the Hg-treated group was significantly higher than that in the control group, causing calcium overload. Through our experiments, the neurotoxic effects of IHg on shellfish were revealed from the perspective of metabolism and neurotransmitters, which provided effective data for the study of the regulatory mechanism of the nervous system in response to environmental stimuli in shellfish and reinforced the use of M. chinensis philippi as a model for the evaluation of environmental quality in aquatic ecosystems. This paper has not been published yet