Aberrant protein glycosylation may reflect changes in cell metabolism of type II diabetes mellitus (T2DM) and offers fresh vistas for discovering potential biomarkers. However, the functional significance of T2DM N-glycan alterations is underexplored, since to date, N-glycan profiling studies have been performed in selected populations. Geographically and genetically isolated populations are needed for validation of specific biomarkers. This age-sex matched cross sectional study comprising 232 T2DM patients and 219 controls was conducted in Ghana, Western Africa. Blood plasma samples were collected for clinical assessment after which plasma N-glycans were freed and analysed by ultra-performance liquid chromatography (UPLC). High branching (HB) W = 46328; q = 0.00072, tri-galactosylated (G3) W = 44076; q = 0.00096, antennary fucosylated (FUC_A) W = 43055; q = 0.0000763, and triantennary (TRIA) W = 44624; q = 0.0025, N-glycan structures were increased in T2DM whereas low branching (LB) W = 46328; q = 0.00072, non-sialylated (S0) W = 46929; q = 0.00292, monogalactosylation (G1) W = 44091; q = 0.0000763, core fucosylation (FUC_C), W = 46497; q = 0.00096, biantennary galactosylation (A2G) W = 45663; q = 0.000763, and biantennary (BA) W = 46376; q = 0.00072, structures were decreased compared to controls. Nine N-glycan peaks (GPs (GP1, GP4, GP7, GP11, GP17, GP19, GP22, GP26, GP29)) were found to predict case status based on Akaike's information criterion (AIC) and Bayesian information criterion (BIC) model selection. Adjusting for age, sex and other co-variates in this model yielded an area under the curve (AUC) of 80.5% with sensitivity of 79% and specificity of 73%, indicating the predicting power of N-glycans as robust biomarkers. Our results show that hyperglycemia influences N-glycan complexities among Ghanaians. N-glycan profiling in distinct populations has affirmed the potentiality of N-glycan profiles as generic biomarkers which may facilitate better prognosis for T2DM. •T2DM was associated with a decreased core fucosylated plasma N-glycans.•T2DM was associated with decreased low-branching plasma N-glycans.•T2DM was associated with increased high branching plasma N-glycans.•T2DM was associated with increased disialylated and trisialylated plasma N-glycans.•The area under the curve was 80.5% indicating the good predicting power of N-glycans.