Randomized controlled trials (RCTs) are a well-established scientific method for building evidence to support the efficacy of an intervention. Proposed metabolic interventions for neuropsychiatric problems range from ketogenic diets to probiotics and omega-3 supplements, among many others. Here, a comprehensive guide is presented for researchers and clinicians to use as they navigate the intricacies of planning, conducting, analyzing, and reporting on clinical trials in metabolic therapies for neuropsychiatric disorders. In-depth topics include the fundamental role of and ways to achieve randomization, trial design decisions, choice of control group and blinding, specification of outcomes including mechanisms of action, power calculations and sample size, as well as the intention to treat and account for lack of adherence. Issues related to ethical oversight, safety monitoring, standardized protocols, preregistration, and adherence to reporting standards (e.g., CONSORT) are presented as integral elements of a clinical trial’s integrity, ensuring reliable and actionable outcomes. The chapter advocates for thoughtfully designed and analyzed RCTs that prioritize scientific rigor alongside clinical relevance.