About 70 officers were involved in the operation which targeted three premises in the Leith Walk, Newington and Wester Hailes areas.
Representatives from Trading Standards and Environmental Health visited a further eight stores as part of the initiative to stem sales of New Psychoactive Substances (NPS) and raise public awareness of their risks.
NPS, which can contain harmful chemicals, have been implicated in dozens of deaths in Scotland in recent years. They are produced to have a similar effect to Ecstasy but fall outside UK drugs laws and have been sold at petrol stations, newsagents and takeaways.
Police Scotland said they seized more than 3,000 sachets of substances, which will now be sent away for analysis.
As part of the campaign, posters are going on display on buses and in train stations warning young people, "Legal doesn't mean safe".
Detective Chief Inspector Stuart Houston said: "Police Scotland is committed to keeping people safe and to stopping the sale of any substances which may cause harm to our communities.
"The items seized during the operation will now be subject to detailed analysis and we will be continuing to engage with our various partner agencies.
"Enforcement is only a small part of this operation and we are keen to educate the public on all the associated risks of NPS so that fewer people are inclined to buy and consume them."