Cytokine storms, oxidative stress, and hyperglycemia can enhance the risk of type 2 diabetes (T2D). Moreover, T2D may change the functional and structural heart. However, some signaling pathways, such as insulin resistance, dyslipidemia, and hyperglycemia, can play in T2D, and various pathomechanics and pathophysiology involved in T2D are not understood. Moreover, it is well documented that the non-coding RNAs are potentially pivotal molecules in oxidative stress, inflammation, and cell death signaling pathways. Hence, long non-coding RNAs (lncRNAs) and microRNAs may have vital roles in oxidative stress, inflammation, metabolism, T2D, and cardiovascular systems. Non-coding RNAs can target hub gene networks and suppress or trigger various cascades. Furthermore, lifestyle is the other factor that may affect the prevalence of T2D. A sedentary lifestyle and excessive sitting can enhance inflammation, oxidative stress, and hyperglycemia. Here, we attempt to comprehend the role of hub genes, non-coding RNAs, and unhealthy lifestyles on the pathomechanics and pathophysiology of diabetic vascular complications.