Background This systematic review evaluates the efficacy, safety, and tolerability of ixekizumab (IXE), an anti-IL 17A monoclonal antibody, in treating moderate to severe psoriasis. Methods A comprehensive search of PubMed and Scopus using the terms ‘ixekizumab’ and ‘psoriasis’ was conducted. This study was registered in PROSPERO (CRD42024539975) and followed the PRISMA guidelines for reporting systematic reviews. Inclusion criteria encompassed randomised clinical trials assessing the efficacy and safety/tolerability of ixekizumab for moderate-to-severe psoriasis, published from inception until April 2024. Case reports, conference papers, and observational studies were excluded. A total of 5 studies (6 randomised controlled trials) with 4705 participants met the selection criteria out of 1172 search results. The risk of bias was assessed among the selected studies using the RoBViS tool. Results The standardised dosing regimen of ixekizumab demonstrated superior efficacy compared to placebo in improving Psoriasis Area and Severity Index (PASI) from baseline and Static Physician Global Assessment (sPGA) across most of the included studies. No significant difference in efficacy was observed when comparing ixekizumab with ustekinumab in a survey conducted by Reich et al. Most adverse events were mild, although some serious ones were reported. Conclusion Ixekizumab, a monoclonal antibody approved for treating moderate to severe psoriasis, exhibits a superior safety profile comparable to other biologics used in psoriasis. However, its widespread usage in psoriasis is still relatively less than conventional non-selective immunomodulatory agents.