Optogenetics and neuropharmacology holds immense promise for dissection of neural circuits and cellular signaling in freely behaving animals. However, the full potential of their in vivo applications is limited by the use of conventional tools such as cannulas for drug delivery and fiber optics for photostimulation. These traditional approaches greatly damage neural tissue near the implant, hinder integration with different modalities, and severely limit the animal’s natural behavior and movement, mainly due to their rigid construction, bulky design, and tethered operation, respectively. Furthermore, current methods lack spatiotemporal control of drug delivery, wireless control, and multi-functionality.To address these fundamental limitations in in vivo neuroscience, we have developed soft wireless optofluidic and optoelectronic implants, which can provide wireless delivery of light and/or drugs in awake, moving animals. The devices consist of ultrathin and flexible probes, which integrate microscale inorganic light-emitting diodes and/or microfluidic channels, and wireless interface with an independent power supply. This design enables compact, lightweight and soft system, thus enabling seamless implantation and operation in the brain without causing disturbance of naturalistic behavior. With integration of smartphone control, replaceable drug cartridges for long-term drug delivery, and wireless energy harvesters for intervention-free charging, they can further facilitate chronic neural interfacing to uncover the basis for brain functions and neuropsychiatric diseases. We have successfully demonstrated chronic wireless capabilities of these devices in freely moving animals that can repeatedly deliver multiple wavelengths of light and drugs for long periods of time to manipulate animals’ behavior. The unique capabilities of the soft wireless implants forecasts their broad utility in chronic in vivo neuropharmacology and optogenetics for various neuroscience research and clinical applications.