The kwaggavygie does best in a greenhouse or on a sunny windowsill. In arid regions, especially summer rainfall areas, it can also be planted outside in a rockery. It should be planted in well-drained soil, and keep in mind that this plant has a relatively long taproot. Pleiospilos nelii should get little water in winter and in summer. Unlike other Pleiospilos species, P. nelii will not flower if it is kept dry in winter. When watering, rather drench the soil and allow the soil to dry out for 2-3 weeks before watering again. The new pair of leaves starts growing in winter. The plant uses the moisture from the old leaves to create the new ones. If the old leaves are still present in summer, this could indicate that the plant might be getting too much water.

Pleiospilos nelii can easily be grown from seeds. Sow seeds in the summer months. To improve the success of germination, place the seeds in a small container with lukewarm water and leave for 24 hours. This will soften the hard outer layer of the seed. Sow the seeds in a sandy medium. Cover the seeds with a 1 mm thick layer of fine sand but make sure that they are not covered too thickly. The layer of sand prevents the tiny seeds from washing away, and it is best to water with a very fine spray. Keep them damp until they start to germinate in about seven days. Once the seedlings start growing, slowly reduce the amount of water given. The seedlings grow very slowly and should be replanted once they have reached a height of about 10 mm.

The kwaggavygie is susceptible to red spider mites that scar the leaf surface with brown markings. Treat with horticultural oil, such as oleum, in a solution of 20 ml oleum to 1 litre of water.