Ischemic stroke is a leading cause of global disability, yet the precise pathogenic mechanisms remain elusive, limiting the effectiveness of treatments. This issue is compounded by animal models that inadequately reflect critical patient characteristics, such as health status and age, and the predominant use of male subjects, despite stroke affecting all genders. Consequently, treatments validated in male-centric models may prove ineffective or even detrimental for females. To gain a comprehensive understanding of sex-specific mechanisms underlying stroke injury, protection, and repair, we are conducting a systematic review of ischemic stroke studies that used animals of both sexes. A protocol detailing the planned methods is registered on PROSPERO (CRD42023495731). We searched Embase via OVID, Web of Science preprint collection, and Stroke-SOLES, a custom-made tool that retrieves studies from PubMed, Scopus, and Web of Science and uses machine learning to filter for animal stroke experiments, thereby accelerating eligibility screening of retrieved studies. 4896 unique records were retrieved, and title/abstract screening by at least two independent reviewers yielded 1396 studies for full-text screening, data extraction, and risk of bias assessment. We will present synthesized evidence on sex differences in stroke severity, treatment efficacy, and underlying mechanisms. We will also report the impact of effect modifiers (e.g., stroke induction techniques) and present risk of bias assessments to highlight the methodological quality of synthesised evidence. Our work seeks to refine the design and translational relevance of future preclinical studies, ultimately contributing to the development of more effective and personalised therapeutic interventions in clinical settings.