Non-steroidal anti-inflammatory drugs (NSAIDs) are one the most commonly prescribed pain killers. NSAIDs can cause adverse health effects on humans such as gastrointestinal disorder, anemia, agranulocytosis and changes in renal functions. Therefore, it is significant to achieve a suitable technique for accurate measuring these compounds. During the last decades, many studies have focused on development of simple, environmentally friendly and efficient miniaturized sample preparation methods with a high clean up ability. In this way, a lot of extraction techniques such as solid phase microextraction (SPME) and electromembrane extraction (EME) have been employed in remarkable number of investigations. As a result of performing two extraction techniques simultaneously, it could be possible to take advantages of both methods. Hence, extraction recoveries, preconcentration factors and other noteworthy extraction features such as ability to clean up through matrix sample could be improved. In this study, Cu/Cr layered double hydroxid was dispersed in poly (methacrilic acid-coethylene glycol dimethacrylate) (MAA-co-EGDMA) polymerization mixture and in-situ polymerization was performed in acceptor phase channel. Thus, a monolithic composite was formed in the channel. Thereafter, EME-SPME on chip was developed to extract naproxen, diclofenac and mefenamic acid from various complex matrices. Likewise, desorbtion step was performed after electromembrane extraction and eluent was injected into high performance liquid chromatography-UV for separation and determination of the drugs. Effective parameters on extraction efficiency were optimized and under optimum conditions, the limit of detections of the mentioned analytes were 0.1-0.25 ng/mL. Linearity of method was obtained within the range of 0.5-500 ng/mL for naproxen and 1-250 ng/mL for dicofenac and mefenamic acid with coefficients of determination greater than 0.996. Under evaluation of this method, extraction recoveries were obtained in the range of 83.34-90.87% which corresponded to preconcentration factors of 56-61. The precision of the method is suitable with relative standard deviations lower than 4.8%. The method was applied for extraction of the drugs from real saples like as breast milk, urine and plasma; and satisfactory results were obtained.