Delirium is a common condition across different settings and populations. The interventions for preventing and managing this condition are still poorly known. The aim of this umbrella review is to synthesize and grade all preventative and therapeutic interventions for delirium. We searched five databases from database inception up to March 15th, 2023 and we included meta -analyses of randomized controlled trials (RCTs) to decrease the risk of/the severity of delirium. From 1959 records after deduplication, we included 59 systematic reviews with meta -analyses, providing 110 meta -analytic estimates across populations, interventions, outcomes, settings, and age groups (485 unique RCTs, 172,045 participants). In surgery setting, for preventing delirium, high GRADE evidence supported dexmedetomidine (RR =0.53; 95%CI: 0.46 -0.67, k =13, N =3988) and comprehensive geriatric assessment (OR =0.46; 95%CI =0.32 -0.67, k =3, N =496) in older adults, dexmedetomidine in adults (RR =0.33, 95%CI =0.24 -0.45, k =7, N =1974), A2-adrenergic agonists after induction of anesthesia (OR = 0.28, 95%CI = 0.19 -0.40, k =10, N =669) in children. High certainty evidence did not support melatonergic agents in older adults for delirium prevention. Moderate certainty supported the effect of dexmedetomidine in adults and children (k =4), various non -pharmacological interventions in adults and older people (k =4), second -generation antipsychotics in adults and mixed age groups (k =3), EEG -guided anesthesia in adults (k =2), mixed pharmacological interventions (k =1), five other specific pharmacological interventions in children (k =1 each). In conclusion, our work indicates that effective treatments to prevent delirium differ across populations, settings, and age groups. Results inform future guidelines to prevent or treat delirium, accounting for safety and costs of interventions. More research is needed in non -surgical settings.