Isotretinoin is an effective treatment against acne vulgaris, but it also causes many side effects during and after the treatment. The relationship between the changes in the levels of plasma trace elements of patients with AV after 3 months of isotretinoin treatment and the side effects was investigated in the study. Plasma samples of 35 patients were collected before and after isotretinoin treatment. Samples were analyzed by Inductively Coupled Plasma–Mass Spectrometer. After treatment, the levels of phosphorus, magnesium, and zinc in plasma increased statistically, while the level of potassium decreased (p < 0.05). The treatment had differing effects on zinc levels based on the gender of the individuals. With treatment, the levels of zinc in the plasma of men showed a greater increase compared to women (p = 7.3e-04). Additionally, the correlation matrix analysis revealed a strong correlation (R > 0.8) between magnesium and calcium. According to the study results, the change in phosphorus and potassium levels shows that isotretinoin affects kidney functions. The results suggest that phosphorus, potassium, magnesium, and zinc are associated with fatigue, dry skin and chapped lips, hair loss, and sebum secretion, respectively. Consequently, the study emphasizes the need for a comprehensive pre-treatment assessment, including monitoring of liver and kidney function as well as the levels of phosphorus and potassium in patients.