Multipath frequency-selective fading can degrade the performance of a wireless communication system significantly as the data rate increases, e.g., when the data rate is as high as those of systems beyond long-term evolution (LTE)-Advanced. An effective method to combat multipath fading is a code division multiple access (CDMA) scheme. The objective of this dissertation is to present an effective method in designing nonbinary, secure, and optimum spreading and despreading pseudo noise (PN) sequences for CDMA multi-relay networks under frequency-selective fading by employing a maximum signal-to-interference-plus-noise ratio (SINR) criterion. This dissertation assumes that channel state information (CSI) is known at a central station such as a cloud radio access network (CRAN), which computes the optimum PN sequences and forwards them to both sources and destinations. This dissertation considers both partially and fully connected relay networks consisting of multiple sources, multiple relays, and multiple destinations. Direct links from sources to destinations are available in fully connected relay networks, whereas they are not available in partially connected relay networks. This dissertation also finds the optimum PN spreading and despreading sequences jointly and iteratively using the proposed novel method for multiple sources and destinations. Furthermore, it examines the sensitivity of the proposed schemes to imperfect CSI and wideband jamming. Simulation results verify that the proposed method can effectively improve system performance and can converge much faster in finding optimum PN sequences jointly for multiple sources and destinations than existing schemes under the same environment.