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Introduction Stroke burden is largely due to long-term impairments requiring prolonged care and loss of productivity. We aim to identify and assess studies of different registered pharmacological therapies as treatments for improving post-stroke impairments and/or disabilities. Methods In a systematic-search-and-review (PROSPERO registration: CRD42022376973), studies of treatments that have been investigated as recovery-enhancing or recovery-promoting treatments in adult patients who had suffered a stroke will be searched for, screened, and reviewed based on the following: Participants (P): adult humans, aged 18 years or older, diagnosed with stroke; Interventions (I): registered or marketed pharmacological therapies that have been investigated as recovery-enhancing or recovery-promoting treatments in stroke; Comparators (C): active or placebo or no comparator; Outcomes (O): stroke-related neurological impairments and functional/disability assessments. Data will be extracted from included papers, including patient demographics, study methods, key stroke inclusion criteria, details of intervention and control, and the reported outcomes. “The best available studies” based on study design, study size, and/or date of publication for different therapies and stroke subtypes will be selected and graded for level of evidence by consensus. Conclusion There are conflicting study results of pharmacological interventions after an acute stroke to enhance recovery. This systematic search and review will identify best evidence and knowledge gaps in the pharmacological treatment of post-stroke patients as well as guide clinical decision-making and planning of future studies.