Background: Parents can be psychologically impacted when children have eye diseases such as blindness, strabismus, and eye cancer. Stress can reduce the quality of parental care, and may be linked to the deterioration of parents’ and children’s mental and physical health, and family dynamics. No systematic literature review on parental stress in ophthalmology has been found to provide evidence synthesis capable of stimulating and defining new studies promoting research in this field. To address this important gap, the present review aims to synthesize evidence about approaches, methods, instruments, and results from research regarding ophthalmology-related parental stress. Methods: Primary epidemiological observational studies should be original in addressing parental stress caused by ophthalmological health conditions in children. Children must be up to 12 years old and should not have any other associated chronic/disabling condition. Studies must present a summary, and full text should be available in a database. They should present an instrument for assessing parental stress and characterizing the study population. MEDLINE (via Ovid), EMBASE, PsycINFO, Google Scholar, and Gray Literature (PsycEXTRA, NTIS and OpenSINGLE) will be searched. Controlled vocabulary, Boolean operators, and defined search strategies will be used. There will be no restrictions on the studies’ publication language, which will be selected in two screening stages. Two reviewers will independently retrieve full-text studies, assess methodological quality, and extract data. Data available through December 2020 will be considered for inclusion. Discussion: The socioeconomic characterization of the participants, the identification of which ophthalmological diseases have been studied in relation to parental stress, and the knowledge of each instrument and methodology peculiarities potentially contribute to this study. The results may promote the development or enhancement of public policies focused on this specific theme, thereby providing the means for potential improvement of physical and mental health for parents and children with eye diseases.Systematic review registration: The review protocol was registered in PROSPERO: number CRD42018094972.