Mitochondria play a critical role in several cellular processes and cellular homeostasis. Mitochondrion dysfunction has been correlated with numerous metabolic diseases such as obesity and type 2 diabetes. MicroRNAs are non‐coding RNAs that have emerged as key regulators of cell metabolism. The microRNAs act as central regulators of metabolic gene networks by leading to the degradation of their target messenger RNA or repression of protein translation. In addition, vesicular and non‐vesicular circulating miRNAs exhibit a potential role as mediators of the cross‐talk between the skeletal muscle and other tissues/organs. In this review, we will focus on the emerging knowledge of miRNAs controlling mitochondrial function and insulin signaling in skeletal muscle cells. J. Cell. Physiol. 232: 958–966, 2017. © 2016 Wiley Periodicals, Inc. Mitochondrion dysfunction in skeletal muscle has been correlated with innumerous metabolic diseases. MicroRNAs have emerged as key regulators of cell metabolism. In addition, vesicular and non‐vesicular circulating miRNAs exhibit potential role as mediators of the cross‐talking between skeletal muscle and other tissues controlling mitochondrial function and insulin signaling.