There is an increasing number of people with Alzheimer’s disease. Negative emotions are not only one of the symptoms of AD, but also the accelerator of the disease. Animal therapy can have a positive impact on the negative emotions of patients, but it has strict requirements for both environments and animals. In this study, we aim to explore the effectiveness of using virtual animals and their impact on the reduction of patients’ negative emotions to improve the user’s cognitive functions. This approach has been implemented in the Zoo Therapy project, which presents an immersive 3D virtual reality animal environment, where the impact on the patient’s emotion is measured in real-time by using electroencephalography (EEG). In addition to creating highly realistic virtual animals, the innovation of Zoo Therapy is also in its communication mechanism as it implements bidirectional human-computer interaction supported by 3 interaction methods: 3D buttons, speech instruction, and Neurofeedback. Patients can actively interact with virtual animals through 3D buttons or speech instructions. The Neurofeedback system will guide the animal to actively interact with the patients according to their real-time emotional changes to reduce their negative emotions. Experiments and preliminary results show that it is possible to interact with virtual animals in Zoo Therapy, and the Neurofeedback system can intervene in Zoo VR environment when the emotional value goes down and might reduce patients’ negative emotions.