The design of high energy Li-ion batteries (LIBs) by coupling high voltage LiNi0.5Mn1.5O4 (LNMO) cathode and Li4Ti5O12 (LTO) anode ensures effective and safe energy-storage. LTO-LNMO full-cells (FCs) with difference in electrode grain sizes and presence of excess Mn3+ in cathode were studied using micron-sized commercial LTO, nanostructured LTO donuts (LTOd), P4332 LNMO nanopowders, and nanostructured Fd3m LNMO caterpillars (LNMOcplr). Among the studied FCs, LTOd-LNMOcplr was detected with a stable capacity of 69 mA h/g (1C rate), 99% coulombic efficiency, and 87% capacity retention under 200 cycles of continuous charge-discharge studies. The superior electrochemical performance observed in LTOd-LNMOcplr FC was due to the low charge transfer resistance, which is corroborated to the effect of grain sizes and the longer retention of Mn3+ in the electrodes. An effective and simple FC design incorporating both nanostructuring and in situ conductivity in electrode materials would aid in developing future high-performance LIBs. © Copyright Materials Research Society 2019.