Background The composition of the tumor microenvironment (TME) is conditioned by immunity and the inflammatory response. Nutritional and inflammation-based risk scores have emerged as relevant predictors of survival outcome across a variety of hematological malignancies. Methods In this retrospective multicenter trial, we ascertained the prognostic impact of established nutritional and inflammation-based risk scores [Glasgow Prognostic Score (GPS), C-reactive–protein/albumin ratio (CAR), neutrophil–lymphocyte ratio (NLR), prognostic nutritional index (PNI), and prognostic index (PI)] in 209 eligible patients with histologically confirmed CD20+ follicular lymphoma (FL) of WHO grade 1 (37.3%), 1–2 (16.3%), 2 (26.8%) or 3A (19.8%) admitted to the participating centers between January 2000 and December 2019. Characteristics significantly associated with overall or progression-free survival (OS, PFS) upon univariate analysis were subsequently included in a Cox proportional hazard model. Results In the study cohort, the median age was 63 (range 22–90 years). The median follow-up period covered 99 months. The GPS and the CAR were identified to predict survival in FL patients. The GPS was the only independent predictor of OS (p < 0.0001; HR 2.773; 95% CI 1.630–4.719) and PFS (p = 0.001; HR 1.995; 95% CI 1.352–2.944) upon multivariate analysis. Additionally, there was frequent occurrence of progression of disease within 24 months (POD24) in FL patients with a calculated GPS of 2. Conclusion The current results indicate that the GPS predicts especially OS in FL patients. Moreover, GPS was found to display disease-specific effects in regard to FL progression. These findings and potential combinations with additional established prognosticators should be further validated within prospective clinical trials.