Under an adequate nitrate supply (BG11), cyanobacterium Synechocystis sp. PCC 6803 has high protein content but a low storage of glycogen and poly(3-hydroxybutyrate) (PHB). In contrast, when deprived of nitrogen (–N), protein synthesis was repressed and the accumulation of glycogen and PHB was remarkably increased. The repressed protein synthesis caused by sulfur deprivation or treatment with chloramphenicol was also found to slightly enhance PHB accumulation in Synechocystis. Thus, the repressed protein synthesis is associated with the increased PHB and glycogen storage. Here, we examined two other antibiotics that inhibit protein synthesis, erythromycin (EM) and streptomycin (SM) for their effect on the accumulation of PHB and glycogen in Synechocystis. Under –N cultivation, 10 μM EM treatment significantly increased the PHB level to 18 % (w/w cell dry weight [DW]) compared to 3 % (w/w DW) in the untreated cells; however, SM treatment did not increase the PHB level. Under BG11 cultivation, exposure to 0.7 μM SM and 5 μM EM enhanced glycogen accumulation up to 15 % and 41 % (w/w DW) respectively, compared to only 7 % (w/w DW) in the untreated cells. The EM treatment also remarkably reduced the total protein and phycobiliprotein contents. Results from metabolomic analysis suggested that EM treatment caused protein degradation into amino acids, some of which were metabolized into substrates that can be used for PHB and glycogen synthesis. This was substantiated by the result showing that EM treated cells had significantly increased levels of both the PHB-synthesizing substrates (acetyl-CoA, acetoacetyl-CoA, and 3-hydroxybutyryl-CoA) when cultured under –N, and the glycogen-synthesizing substrates (fructose-1,6-BP, fructose-6-P, glucose-6-P, glucose-1-P, and ADP-glucose) when cultured in BG11. Therefore, EM treatment might be applicable for enhancing the accumulation of these two biopolymers in other cyanobacteria. © 2023 Elsevier B.V.