Introduction Alcohol dependence syndrome (ADS) is a medical condition characterized by regular and excessive consumption of alcohol. ADS is a brain disorder wherein people consume alcohol despite knowing the physical, social, and financial consequences. Zinc and magnesium are microelements that are essential in the proper functioning of human physiological and biological processes. However, the homeostasis of these microelements' is disturbed among ADS patients. The present study aims to assess Zinc and magnesium activities among ADS patients and age-matched controls. Methods The study included 100 ADS patients and an equal number of the control group and was conducted between August and September 2021. The study was performed after acquiring approval from the institutional ethics committee. All the study cases were patients attending the department of Psychiatry, RVM Institute of Medical Sciences & Research Centre who were diagnosed with ADS. Both groups used the colorimetric method on ERBA Chem 5+ semi autoanalyzer to estimate serum zinc and magnesium levels. Results Among the 100 cases of ADS, 84 (84%) were males, and 16 (16%) were females. Patients were between the age group of 20 and 68 (mean: 42.8 years). Of the 100 controls, 84 (84%) were males, and 16 (16%) were females with a mean age of 43.1 years. The activities of Zinc among ADS patients and the control group were 88.53±18.7 μg/dL and 144.9±38.47 μg/dL (p<0.0001), respectively. The activities of magnesium among the ADS patients and the control group were 1.96±0.46 mg/dL and 2.88±0.4 mg/dL (p<0.0001), respectively. Conclusions The activities of Zinc and magnesium have been noted to be significantly lower among ADS patients. Because both these microelements play a vital role in human cells' metabolic and physiologic activities, therapeutic interventions to compensate for such deficiencies while managing ADS patients may prove beneficial.