A low‐power self‐biased single operational transconductance amplifier (OTA)‐based temperature and offset compensated fully differential instrumentation amplifier (FDIA) is proposed in this article. The design of the FDIA circuit, mainly for low‐frequency applications like wearable bio‐medical instruments, is carried out in SCL 0.18‐m standard CMOS technology. The circuit operates under 0.6V supply voltage. The 43.8dB differential gain of the FDIA demonstrates a maximum variation of 47 mdB/°C for temperature ranging between °C and +48°C with signal‐bandwidth ranging from 0.5 to 1.02 kHz. It also shows a moderately high common mode rejection ratio (CMRR) of 100 dB. A simple offset‐compensation arrangement lowers the offset voltage to only 13 nV which drifts maximum by 425 pV/°C. Operation under sub‐1 V supply voltage, nano‐ampere bias currents, and weak inversion mode of operations of the transistors has effectively restricted the power consumption of the proposed FDIA circuit to less than 500 nW. An optimized layout design of the proposed circuit results in a total silicon area of 0.014 mm.