Background: Diabetic polyneuropathy (DPN) is the major microvascular complication of type 2 diabetes mellitus (T2DM). Painful-DPN is a major cause of mortality as well as morbidity. Long non-coding RNAs (lncRNAs) and microRNAs (miRNA) have emerged as critical regulators of many diseases, however, little is known about their expression patterns and functions in T2DM and its complications. Objective: To investigate the expression profile levels of lncRNA MALAT-1 and miRNA-9 in Egyptian patients with T2DM and to explore their associations with clinical and electrophysiological tests of both painful and painless DPN. Patients and Methods: This cross-sectional controlled study enrolled 55 patients with DPN and 40 controls. All participants were subjected to a complete neurological examination and electrophysiological tests involving nerve conduction studies. The expression levels of lncRNA MALAT-1 and miRNA-9 were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The relative expression levels of MALAT-1 and miRNA-9 were significantly upregulated in patients with DPN (0.219±0.061, 0.006454±0.0018, respectively) compared to controls (0.111±0.013, 0.0033±0.004, respectively). Interestingly, the relative expression levels of MALAT-1 and miRNA-9 were significantly upregulated in patients with painful DPN (0.206±0.037, 0.0045±0.0008, respectively) compared to patients with painless DPN 0.219±0.083, 0.0058±0.0017, respectively). Patients with DPN had sensory-motor axonal polyneuropathy which was affecting both lower limbs more than upper limbs. P<0.001*. Conclusions: The relative expression levels of MALAT-1 and miRNA-9 were significantly upregulated in patients with DPN more specifically in patients with painful DPN groups, hence, MALAT-1 and miRNA-9 could be used as useful and reliable diagnostic biomarkers of DPN