Palmoplantar pustular psoriasis (PPPP), or palmoplantar pustulosis (PPP), is a type of psoriasis that affects the skin on the palms and soles. It is characterised by dermatosis and small sterile pustules and is considered a significant burden on patients' quality of life, as there is currently no gold standard treatment or cure. This network meta-analysis (NMA) compares the efficacy and safety of biologic and non-biologic medications for PPPP and PPP. Medline, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. The efficacy and safety of all medications were assessed through a frequentist NMA using a random-effects model. Treatments were ranked using the net rank function, yielding P scores. Fourteen RCTs with 1056 participants were included. Guselkumab 100 mg was the most effective for improving PPPGA scores (p = 0.72, RR = 1.31, CI: 0.31-5.57). Guselkumab 100 mg was ranked the highest for achieving PPPASI-75 (RR = 5.4, CI: 1.26-23.2, p = 0.023). Oral cyclosporine 1 mg/kg/day was ranked the highest for PPPASI-50 (RR = 2.10, CI: 0.65-6.82). Etretinate 1 mg/kg/day had the highest rate of adverse events (RR = 1.78, CI: 0.92-3.44). Secukinumab 300 mg was associated with the highest rate of serious adverse events (RR = 1.58, CI: 0.21-12.02). Based on the P-scores from our NMA, guselkumab 100 mg was the most effective for PPPGA improvement, guselkumab 100 mg for PPPASI-75, oral cyclosporine 1 mg/kg/day for PPPASI-50, etretinate 1 mg/kg/day had the most adverse events, and secukinumab 300 mg was associated with the highest rate of serious adverse events. TRIAL REGISTRATION: PROSPERO registration number: CRD42023460842.