The purpose of this study was to evaluate the effect of nutritional-deficiency anemia (NDA) on peripapillary retinal nerve fiber layer thickness (PPRNFLT) using spectral-domain optical coherence tomography and to determine any correlation arising thereof. This was a single-center, cross-sectional, observational study. A total 115 eyes of 115 NDA patients (50 of each with iron-deficiency anemia [IDA] and Vitamin B12-deficiency anemia [BDA], and 15 with folic acid-deficiency anemia [FDA]) aged 18-65 years were compared with a total 100 eyes of 50 age- and sex-matched healthy controls. All subjects underwent comprehensive clinical, ophthalmic, and hematological evaluation, followed by PPRNFLT assessment for the mean total, superior, inferior, nasal, and temporal quadrants. PPRNFLT for the mean total and all four quadrants in IDA patients, for the mean total, inferior, nasal, and temporal quadrants in BDA patients, and for the mean total, inferior, and nasal quadrants, in FDA patients, was significantly lower as compared to the controls (P < 0.05). The mean total PPRNFLT of all NDA patients correlated significantly (P < 0.05) with their relevant hematological parameters with Pearson's coefficient (r) value of 0.613, 0.610, 0.336, 0.295, 0.337, 0.374, and - 0.509, respectively, for serum haemoglobin (Hb), iron, ferritin, mean corpuscular volume (MCV), mean cell hemoglobin, mean corpuscular hemoglobin concentration, and total iron binding capacity in IDA; 0.310, 0.435, and - 0.386, respectively, for serum Hb%, Vitamin B12, and MCV in BDA; and 0.557, 0.358, and - 0.294 for Hb%, folate, and MCV, respectively, in FDA cases. Mean total retinal nerve fiber layer thinning of all NDA patients showed progression with the increasing severity grades of anemia, except in very severe BDA where an inverse relationship was documented. Our study revealed that PPRNFLT is significantly thinner in all NDA patients (total and all four quadrants in IDA; total, inferior, nasal, and temporal in BDA; and total, inferior, and nasal in FDA) correlating well with their relevant hematological parameters. Early detection of this may be crucial in preventing potential blinding sequelae and differentiating glaucomatous and other neuro-ophthalmic disorders.