Several treatment modalities for palmoplantar warts (PPW) have been introduced, but none have been proven to be significantly effective in all patients. The study aims to assess the efficacy and safety of cryotherapy compared to other modalities for PPW. Searches were conducted in Medline, Embase, Scopus, and CENTRAL databases, along with additional reference and citation tracking from included studies. Randomized controlled trials (RCTs) comparing various treatments for PPW were included. Two independent pairs extracted the data from the included studies. Outcomes assessed included cure rates, pain scores, recurrence rates, and adverse events. A network meta-analysis using Netmeta in R software was employed, with treatments ranked by p-scores. A total of 27 RCTs that enrolled 2539 participants were deemed eligible. As per p-scores, needling yielded the highest odds for the cure rate (p=1.00), followed by intralesional injection of the measles, mumps, and rubella (MMR) vaccine (p=0.90). For the pain score, 76% topical monochloroacetic acid (p=0.13) showed the lowest mean pain score, while cryotherapy yielded the highest score (p=0.90). Furthermore, cryotherapy showed the highest odds for recurrence rate (p=0.75), followed by intralesional injection of Candida antigen (p=0.61). Regarding adverse events, 0.05% intralesional bleomycin had the highest rate (p=0.93), followed by cryotherapy (p=0.61).