Psoriasis is a chronic skin disease that affects a significant number of patients and can severely impair quality of life. Although the diagnosis is normally clinical, paraclinical determination can occasionally be useful either in differential diagnosis or in evaluating the inflammatory response to treatment. MicroRNAs (miRNAs) are small non-coding parts of the RNA family that regulate gene expression and may have an important role as biomarkers in evaluating treatment response. The dysregulation of miRNAs has been well studied in other diseases, especially in oncology, but their role in chronic skin conditions such as psoriasis is still not fully understood. This study aims to evaluate the levels of three miRNAs (miR-155, miR-210, and miR-205) in patients with psoriasis, treated either systemically or topically, compared to a control group, and to assess the possible relationship between miRNA levels and systemic therapy. Our findings show a constant dysregulation of miR-205 in patients with psoriasis, with significantly higher levels compared to the control group, which can be explained as conferring a protective effect to treated patients. Further studies are needed in order to fully understand the role of miRNAs in the physiopathology of psoriasis and even, potentially, to provide more targeted genetic therapies in the future.