Jellyfish stings and envenomation can cause local and systemic symptoms with varying severity and duration. The goals of first aid include interventions to relieve symptoms, thus reducing morbidity and mortality. In this systematic review performed on behalf of the International Liaison Committee on Resuscitation (ILCOR) First Aid Task Force, we aimed to answer the question: Among adults and children with a suspected jellyfish sting, what is the effect of first aid intervention as treatment, compared to other treatment or no treatment, on pain, time to pain relief, survival, need for hospitalization, and adverse outcomes or complications? A search for randomized controlled trials (RCTs) and non-randomized studies was performed on Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (Embase), and Web of Science until 31 March 2025. This systematic review was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions, and reporting adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. There were seven RCTs or quasi-RCTs and three non-randomized studies. There was very low confidence in the estimate of effects for the outcomes evaluated due to the risk of bias and heterogeneity. Treatment with topical vinegar was the most frequently evaluated intervention (seven studies), followed by heat therapy (six studies). All studies reported on the critical outcome of any pain relief and intensity of pain, with a wide range of time to pain relief of up to 24 hours. Adverse outcomes after treatment were evaluated in six studies and included pain, erythema, burns, and difficulty with application. Treatments that may relieve symptoms of jellyfish stings include seawater, heat therapy, cold packs, lidocaine, benzocaine, Adolph's meat tenderizer, vinegar, commercial products (e.g., Stingose or Sting-Aid), and sodium bicarbonate. There were very few studies and a significant risk of bias and heterogeneity, leading to very low-quality evidence on first aid treatment for jellyfish stings. Seawater would be recommended, given its availability at no cost in the coastal region.